Fisiopatologia, diagnòstic i noves estratègies terapèutiques - Dialnet

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Fisiopatologia, diagnòstic i noves estratègies terapèutiques per a la disfàgia orofaríngia neurògena o associada a l’envelliment Tesi doctoral presentada per Laia Rofes i Salsench per optar al grau de Doctor Programa de Doctorat en Medicina (UAB) Maig del 2014

CIBEREHD Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas Instituto de Salud Carlos III UNIVERSITAT AUTÒNOMA DE BARCELONA Facultat de Medicina Departament de Medicina HOSPITAL DE MATARÓ Consorci Sanitari del Maresme Unitat d’Exploracions Funcionals Digestives

Directors: Dr. Pere Clavé Civit i Dr. Joan Monés Xiol Tutor: Dr. Carlos Guarner Aguilar

PERE CLAVÉ i CIVIT, Director Acadèmic, de Recerca i Innovació i Cap de la Unitat d’Exploracions Funcionals Digestives de l’Hospital de Mataró (Consorci Sanitari del Maresme), Professor Associat del Departament de Cirurgia de la Universitat Autònoma de Barcelona i IP del grup CIBERehd CSdM-UAB.

JOAN MONÉS i XIOL, Profesor Emèrit de Medicina i Bioètica de la Facultat de Medicina de la Universidad Autònoma de Barcelona.

FAN CONSTAR: Que la memòria titulada “Fisiopatologia, diagnòstic i noves estratègies terapèutiques per a la disfàgia orofaríngia neurògena o associada a l’envelliment” presentada per LAIA ROFES i SALSENCH per optar al grau de Doctor, duta a terme al Grup de Recerca CIBERehd de l’Hospital de Mataró, s’ha realitzat sota la nostra direcció, i al considerar-la finalitzada, autoritzem la seva presentació per a ser avaluada pel Tribunal corresponent.

I per a que consti a tals efectes signem la present, Hospital de Mataró, 15 de maig del 2014

Dr Pere Clavé i Civit

Dr Joan Monés i Xiol

Dr Carlos Guarner Aguilar

Director de la Tesi

Co-Director de la Tesi

Tutor de la Tesi

A mons pares

Retxes de sol atravessen blaus marins, ses algues tornen verdes i brillen ses estrelles, que ja s’ha fet de nit i es plàncton s’il·lumina i canten ses sirenes aproximadament per no existir. -

Joan Miquel Oliver

Agraïments

Agraïments Finalment ha arribat el moment de posar el punt i final a aquesta etapa de formació i desenvolupament, no només professional sinó també en gran part personal. És el moment de fer una parada en el camí, mirar enrere i fer balanç. Perquè són moltes les experiències viscudes i diversa la gent amb les que les he compartit i que, en major o menor mesura, m’han ajudat a arribar fins aquí. És per això que voldria aprofitar aquestes línies per transmetre el meu agraïment a totes aquestes persones que en part, han fet possible aquesta Tesi. Primer de tot voldria agrair al Dr Pere Clavé la oportunitat que em va donar per realizar aquesta Tesi, per confiar en mi en aquell moment, però sobretot per haver-me permès evolucionar al llarg d’aquests anys. Per fomentar el meu esperit crític, escoltar les meves opinions i donar-me les teves, pels debats i discussions que fan de la ciència un camp estimulant. Per totes les hores (que han estat moltes!) que has dedicat a deshores a planificar, discutir i revisar els estudis realitzats. Gràcies Pere. Als Drs. Joan Monés i Carlos Guarner, per acceptar co-dirigir i tutoritzar aquesta Tesi. Per la bona disposició i amabilitat que han tingut sempre amb mi i pels bons consells donats. A la Viri, per tot el que m’ha ensenyat. Perquè la teva ajuda, treball i predisposició del primer a l’últim dia, han estat necessaris, fonamentals, imprescindibles! Per fer això possible. Gràcies per tot. A l’Alberto, per la seva contribució en la realització i anàlisi de les videofluroscòpies i fer-ho sempre de bon humor. A la Irene, per tota la teva ajuda en gairebé tot, per ser sempre tant resolutiva! Perquè sempre t’has implicat fins i tot més del que et tocava. A la Cristina, l’Eli, el Dr Mateu Serra i la Berta. Per haver-me acollit amb els braços oberts a la Unitat de Recerca el meu primer any, pels esmorzars, dinars i voltes a l’Hospital compartides parlant de Catalunya i el món. A la Cristina i a la Berta els hi voldria agrair també el seu suport, eficiència i rapidesa en realitzar qualsevol tipus de gestió que ha estat necessària, que en el país de la burocràcia, no són poques. A l’Eli i al Mateu, els hi voldria agrair la seva contribució als Capítols 2 i 3, el suport metodològic i estadístic que sempre m’han donat, i per ajudar-me a resolder tots els dubtes que em venien al cap. A la Dra Silvia Carrión per les estones compartides a Motilitat, i per la col·laboració en els estudis de Nestlé. Al Dr Almirall, per la seva contribució en el Capítol 2 i especialment, el Capítol 3 de la Tesi. I per haver acceptat formar part del meu tribunal de seguiment. Als Drs Cabré i Palomeras, a la Marisa Sebastián, a l’Anna Ciurana i demés metges i infermeres de planta de l’Hospital de Mataró que ens han ajudat en el reclutament de pacients i instauració dels protocols de disfàgia a l’Hospital. Al Dr Marcel Jiménez i professors del Departament de Fisiologia de la Facultat de Veterinària de la UAB pel bon tracte donat quan vaig estar al 143 fent Calcium Imaging. I també a la Míriam, amb qui vaig compartir aquells primers experiments.

Agraïments ____________________________________________________________________ A la Diana, la Bego i l’Àlvaro. Perquè vosaltres més que ningú sabeu el que és fer aquest camí. Per les teràpies de grup del Beer Club. Per ser-hi per compartir els bons moments, però sobretot els no tant bons. Diana, perquè tens un cor enorme i sempre estàs disposada a ajudar, pels riures compartits (com la nit dels mojitos i els xistes!), pel teu suport sempre que l’he necessitat, per les lluites (infructuoses) lliurades. Bego, per totes les hores compartides a l’Hospital, per donar-me suport quan ho necessitava, sempre tenies un bon consell per donar, perquè feies molt fàcil treballar al teu costat, pels riures a l’Abadía de Melk ;) , per enganxar-me (una mica...) la teva precaució amb els arxius i les còpies de seguretat que m’ha permès arribar fins aquí sense patir cap catàstrofe informàtica (creuem els dits!) i per introduir-me en el món de la doble columna. Álvaro, porque siempre ponías ese punto de cordura cuando la situación se volvía histriónica. A la Jane, per totes les correccions de l’anglès dels abstracts, manuscrits i demés, per ajudar-me a preparar les presentacions dels congressos. Per transmetrem la teva tranquil·litat quan jo la perdia. A la Marisa, pels seus experimentats consells. Als companys del laboratori, Omar, Dani, Natàlia, Lluís, Irene. I a la Mónica! Per compartir els últims anys de la tesi. Pels happy Tuesday. Per descobrir-me Mataró fora de l’Hospital (i les Santes!). Per formar un grup fantàstic amb qui dóna gust treballar. A la Clàudia, per somriure sempre, ets un sol. Al Jakub, per les converses en anglès. A la Sandra i a la Raquel, perque tot i que la distància (no només quilomètrica) ens hagi anat separant, vau ser fonamentals per arribar a la línia de sortida. A la Maria José, per revisar l’ortografia del castellà de la Tesi. I pel suport que junt amb el Sebastià sempre m’heu donat. A mons pares i a mons germans. Pel vostre suport incondicional. A la mama, per ser tot amor. Al papa, per encomanar-me la teva racionalitat i la passió per la ciència i les coses ben fetes, per entendrem quan t’explico les coses. Al Ricard, perquè m’omple d’orgull cada vegada que em diuen que m’assemblo a tu. A la Núria, per ser pilar fonamental, eix vertebrador, fins i tot davant les situacions més adverses, perquè ets la persona més forta que conec. A la Magda i al Marc. Als petits, la Laia, el Guilem, el Bernat i l’Oriol perquè sou l’al·legria de la casa, i al Pol i a l’Aran, per donar-nos la oportunitat de conèixe-us i una lliçó de lluita i de vida. Al Manel, parella, company i amic. Perquè aquest camí també ha estat el nostre. Per creure en mi més que ningú.

Laia

Publicacions

Llista de Publicacions Els capítols que formen el cos d’aquesta Tesi Doctoral han estat publicats o estan pendents de publicació a les següents revistes:

CAPÍTOL 1 Rofes L, Arreola V, Mukherjee R, Clavé P. Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia. Under review in Neurogastroenterol Motil (accepted with Major Revision). CAPÍTOL 2 Rofes L, Arreola V, Romea M, Palomera E, Almirall J, Cabré M, Serra-Prat M, Clavé P. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010; 22(8): 851-8, e230. CAPÍTOL 3 Almirall J*, Rofes L*, Serra-Prat M, Icart R, Palomera E, Arreola V, Clavé P. Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly. Eur Respir J 2013; 41(4): 923-8. *Co-first authors. CAPÍTOL 4 Rofes L, Arreola V, Mukherjee R, Swanson J, Clavé P. The effects of a xanthan gum-based thickener on the swallowing function of patients with dysphagia. Aliment Pharmacol Ther 2014; In press. doi: 10.1111/apt.12696 CAPÍTOL 5 Rofes L, Arreola V, Martin A, Clavé P. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia. Gut 2013; 62(9):1280-7. CAPÍTULO 6 Rofes L, Arreola V, Martin A, Clavé P. Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia. J Gastroenterol 2013; In press. doi:10.1007/s00535-013-0920-0 CAPÍTOL 7 Rofes L, Arreola V, López I, Martin A, Sebastián M, Ciurana A, Clavé P. Effect of surface sensory and motor electrical stimulation on chronic poststroke oropharyngeal dysfunction. Neurogastroenterol Motil 2013; 25(11):888-e701.

Publicacions____________________________________________________________________

Presentacions a congressos i publicacions en forma d’abstract Pathophysiology of oropharyngeal dysphagia in the Frail Elderly. Rofes L, Arreola V, Romeo M, Palomera E, Cabré M, Serra-Prat M, Clavé P. 2008 Joint International Meeting in Neurogastroenterology and Motility (Lucerne, Switzerland, 6-9 de novembre del 2008). Neurogastroenterol Motil 2008; 20(Suppl 2):41 Patofisiologia de la disfàgia orofaríngia en ancians fràgils. Rofes L, Arreola V, Romeo M, Palomera E, Cabré M, Serra-Prat M, Clavé P. XVIII Congrés de la Societat Catalana de Digestologia (Blanes, 29-31 de gener del 2009). Suplements dels Annals de Medicina 2009; 92(Supl 1):S1-62 Tratamiento de la disfagia orofaríngea mediante estimulación de TRPV1. Rofes L, Arreola V, Clavé P. Semana de las Enfermedades Digestivas 2010 (Santiago de Compostela, Spain, 19-22 de juny del 2010). Rev Esp Enferm Dig 2010; 101(Supl I):3 Pharmacological treatment of oropharyngeal dysphagia through TRPV1 stimulation. Rofes L, Arreola V, Clavé P. 2010 Joint International Meeting in Neurogastroenterology and Motility (Boston, USA, 26-29 d’agost del 2010). Neurogastroenterol Motil 2010; 22(Suppl 1):3 L’estimulació de TRPV1 amb capsaicinoids millora la deglució dels pacients amb disfàgia orofaríngia. Rofes L, Arreola V, Clavé P. XX Congrés de la Societat Catalana de Digestologia (Lleida, 27-29 de gener del 2011). Suplements dels Annals de Medicina 2011; 94(Supl 1):S1-36 TRPV1 stimulation with capsaicinoids improves swallow response in dysphagic patients. Rofes L, Arreola V, Clavé P. 2011 Dysphagia Research Society Annual Meeting (San Antonio, USA, 3-5 de març del 2011). Dysphagia 2011; 26:432.

High prevalence of aspirations and delayed swallow response in older patients with community acquired pneumonia. Rofes L, Almirall J, Serra-Prat M, Icart R, Arreola V, Palomera E, Clavé P. 1st Congress of the European Society of Swallowing Disorders (Leiden, The Netherlands, 8-10 de setembre del 2011). Dysphagia 2011; 26:477 Piperine improves swallow response of patients with neurogenic dysphagia. Rofes L, Arreola V, Casamitjana F, Enrique A, Clavé P. 2012 Dysphagia Research Society Annual Meeting (Toronto, Canada, 7-10 de març del 2012). Dysphagia 2012; 27:569-620 Piperine improves swallow response of patients with neurogenic dysphagia. Rofes L, Alvarez D, Arreola V, Casamitjana F, Enrique A, Clavé P. 2012 Joint International Meeting in Neurogastroenterology and Motility (Bologna, Italy, 6-8 de setembre del 2012). Neurogastroenterol Motil 2012; 24(Suppl 2):137

Publicacions Therapeutic effect of xanthan gum-based thickener on swallowing function in patients with oropharyngeal dysphagia. Rofes L, Arreola V, Mukherjee R, Clavé P. 34th ESPEN Congress on Clinical Nutrition and Metabolism (Barcelona, 8-11 de setembre del 2012). Clin Nutr 2012; 7(Suppl 1):257

Diagnostic accuracy of the eating assessment tool and the volume-viscosity swallow test for clinical screening and assessment of oropharyngeal dysphagia. Rofes L, Arreola V, Mukherjee R, Clavé P. 34th ESPEN Congress on Clinical Nutrition and Metabolism (Barcelona, 8-11 de setembre del 2012). Clin Nutr 2012; 7(Suppl 1):256

Therapeutic effect of xanthan gum-based thickener on swallowing function in patients with oropharyngeal dysphagia. Rofes L, Arreola V, Mukherjee R, Clavé P. 20th United European Gastroenterology Week (Amsterdam, Netherlands, 20-24 d’octubre del 2012). Gut 2012; 61(Suppl 3):A429

Diagnostic accuracy of the eating assessment tool and the volume-viscosity swallow test for clinical screening and assessment of oropharyngeal dysphagia. Rofes L, Arreola V, Mukherjee R, Clavé P. 20th United European Gastroenterology Week (Amsterdam, Netherlands, 20-24 d’octubre del 2012). Gut 2012; 61(Suppl 3):A17

L’estimulació elèctrica transcutània millora la seguretat de la deglució en pacients amb disfagia orofaríngia després d’un ictus. Rofes L, Arreola V, López I, Martin A, Sebastián M, Ciurana A, Clavé P. XXII Congrés de la Societat Catalana de Digestologia 2013 (Tarragona, 31 de gener – 2 de febrer del 2013). Suplements dels Annals de Medicina 2013; 96(Supl 1):S1-43

Sensory transcutaneous electrical stimulation improves safety of swallow in post-stroke dysphagic patients Rofes L, Arreola V, Lopez I, Martin A, Sebastián M, Ciurana A, Clavé P. 2013 Dysphagia Research Society Annual Meeting. (Seattle, USA, 14-16 de març del 2013). Dysphagia 2013; 28:610

Beques i Premis_________________________________________________________________

Beques Els estudis que formen part d’aquesta Tesi Doctoral s’han finançat amb les següents beques i projectes: -

Fondo de Investigación Sanitaria (Instituto de Salud Carlos III, Ministerio de Economia y Competitividad): PI/051554 i PS09/01012

-

Col·legi Oficial de Farmacèutics de Barcelona: Beca Col·legial 2009-2010

-

Filial del Maresme de l’Acadèmia de Ciències Mèdiques de Catalunya i Balears: Beca Hospitalària i Sociosanitària 2011

-

Nestlé Health Science: Trial Nº 09.35.CLI

Durant el desenvolupament de la Tesi Doctoral, el salari de l’autora ha estat finançat pel Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd, Instituto de Salud Carlos III). L’autora vol agraïr el suport econòmic rebut de les diferents entitats.

Premis rebuts Millor Comunicació Oral al XXII Congrés De la Societat Catalana de Digestologia 2013 (Tarragona) pel treball: L’estimulació elèctrica transcutània millora la seguretat de la deglució en pacients amb disfagia orofaríngia després d’un ictus. National Scholar Award 2012 (Spain) a la 20th United European Gastroenterology Week (UEGW 2012, Amsterdam, The Netherlands) pel treball: Diagnostic accuracy of the eating assessment tool and the volume-viscosity swallow test for clinical screening and assessment of oropharyngeal dysphagia. Young Clinician-Scientist Travel Grant a la 20th United European Gastroenterology Week (UEGW 2012, Amsterdam, The Netherlands) pel treball: Diagnostic accuracy of the eating assessment tool and the volume-viscosity swallow test for clinical screening and assessment of oropharyngeal dysphagia. Young Investigator Award al 2010 Joint International Meeting in Neurogastroenterology and Motility (Boston, USA) pel treball: Pharmacological treatment of oropharyngeal dysphagia through TRPV1 stimulation.

Resumen Resumen de la Tesis Doctoral La disfagia orofaríngea es un trastorno digestivo reconocido por la Organización Mundial de la Salud (OMS) en la International Classification of Diseases (ICD-10, código R-13) caracterizado por la dificultad para formar y/o mover el bolo alimentario de la boca al esófago, y que puede ocasionar el paso de alimento a la vía respiratoria. Es un trastorno muy prevalente en pacientes con enfermedades neurológicas y de edad avanzada, que se asocia a graves complicaciones respiratorias y nutricionales con una alta morbimortalidad. A pesar de ello, la disfagia orofaríngea continúa siendo un trastorno infradiagnosticado e infratratado. Es importante por lo tanto profundizar en el conocimiento de la fisiopatología de las alteraciones de la deglución y las complicaciones que conllevan, así como mejorar las herramientas diagnósticas y en especial, abrir las puertas a nuevas alternativas de tratamiento, hasta el momento escasas y centradas en mecanismos compensatorios. El primer objetivo de esta Tesis Doctoral ha sido evaluar la validez diagnóstica de una herramienta de cribado (el cuestionario Eating Assessment Tool-10, EAT-10) y el método de exploración clínica volumen-viscosidad (MECV-V). Ambos métodos mostraron una alta sensibilidad y especificidad para detectar aquellos pacientes con alteraciones deglutorias. Posteriormente, hemos caracterizado el patrón motor deglutorio de dos fenotipos de ancianos en alto riesgo de padecer disfagia orofaríngea: el anciano frágil y el anciano con neumonía adquirida en la comunidad. Observamos como el factor fisiopatológico crítico que condicionaba la alteración de la seguridad de la deglución en ambos grupos era un retraso en el tiempo de cierre del vestíbulo laríngeo y en el movimiento vertical del hioides, mientras que una débil fuerza de propulsión condiciona la aparición de residuo orofaríngeo. Estas alteraciones son los factores clave en los que se debería focalizar el desarrollo de las nuevas estrategias terapéuticas. Por otro lado, describimos que la disfagia es un factor de riesgo para la neumonía adquirida en la comunidad en el anciano y un factor de mal pronóstico clínico en los dos fenotipos de ancianos, resaltando la relevancia de la patología y la necesidad de intervención. Es en este sentido que hemos evaluado tres grupos de nuevas estrategias terapéuticas: un tratamiento compensador (espesantes de goma xantana); un tratamiento de neuro-estimulación (agonistas de los canales TRP); y un tratamiento de neuro-rehabilitación periférica (estimulación eléctrica transcutánea). Los espesantes de goma xantana mostraron un efecto terapéutico concentración-dependiente en la prevención de penetraciones y aspiraciones, y un mecanismo de acción secuencial: a viscosidad néctar, el aumento de la seguridad de la deglución puede atribuirse a las características intrínsecas del bolo; a viscosidad pudin, el efecto terapéutico fue mayor debido al enlentecimiento de la velocidad del bolo por la orofaringe. Cabe destacar que no aumentó significativamente del residuo orofaríngeo debido al incremento de la viscosidad. Por otro lado, la suplementación del bolo alimentario con el agonista TRPV1 (capsaicina), y el agonista dual TRPV1/A1 (piperina) acortó el tiempo de cierre del vestíbulo laríngeo, reduciendo así la prevalencia de penetraciones. La capsaicina, además, también mejoró la eficacia de la deglución. La estimulación eléctrica transcutánea aplicada a una intensidad de estimulación sensorial, sin producir la contracción muscular, acortó el tiempo de cierre del vestíbulo laríngeo, reduciendo las alteraciones de la seguridad de la deglución; al aplicar una intensidad de estimulación motora, también redujo el residuo orofaríngeo además de mejorar la seguridad de la deglución. Los estudios de esta Tesis Doctoral confirman que es posible diagnosticar y tratar de forma eficaz a los pacientes con disfagia orofaríngea y abren una nueva línea de investigación destinada a cambiar el enfoque de la terapéutica de la disfagia de la compensación a la recuperación de la función.

Summary_______________________________________________________________________ Summary of the Doctoral Thesis Oropharyngeal dysphagia is a digestive disorder characterized by the difficulty to form or move the bolus from the mouth to the oesophagus and can cause tracheobronchial aspirations. Oropharyngeal dysphagia is classified by the World Health Organization (WHO) in the International Classification of Diseases (ICD-10, code R-13). It is a highly prevalent disorder in patients with neurological diseases and aging, and is associated with serious complications with high morbidity and mortality. Despite this, oropharyngeal dysphagia remains poorly understood, underdiagnosed and undertreated. It is therefore important to further our knowledge of swallowing disorders and associated complications, improve diagnostic tools and, in particular, open doors to new treatments which are currently limited and mainly focused on compensatory mechanisms. The first objective of this thesis was to establish the diagnostic validity of a screening tool (Eating Assessment Tool -10 questionnaire, EAT- 10) and a method of clinical examination, the Volume Viscosity Swallow Test (V-VST). Both methods showed high sensitivity and specificity for detecting patients with swallowing impairment. Then we characterized the swallowing pattern of two phenotypes of elderly patients at high risk of deglutition disorders: frail elderly and elderly patients with community-acquired pneumonia. We observed that delayed laryngeal vestibule closure time and vertical hyoid movement were critical factors in determining the alteration of swallowing safety in these patients, while weak bolus propulsion determined the presence of oropharyngeal residue. So, these were the key factors we targeted in the new treatments. Furthermore, we described how oropharyngeal dysphagia was a risk factor for community-acquired pneumonia in the elderly, and an indicator of bad prognosis in both phenotypes of elderly patients, signalling the severity of the pathology and the need for intervention. We thus evaluated three groups of new therapeutic strategies for patients with oropharyngeal dysphagia: compensatory treatment with a xanthan gum thickener; peripheral neuro-stimulation treatment with TRP agonists, and peripheral neuro-rehabilitation treatment with transcutaneous electrical stimulation. Xanthan gum thickeners had a concentration-dependent effect that prevented penetrations and aspirations. The thickener presented a sequential mechanism of action: at nectar viscosity, the increase in the safety of swallow could be attributed to the intrinsic characteristics of the bolus; at pudding viscosity, where the therapeutic effect was maximum, the slower bolus velocity through the oropharynx contributed to the observed effect. Notably, increasing bolus viscosity did not significantly increase oropharyngeal residue. Bolus supplementation with the TRPV1 agonist capsaicin or the dual TRPV1/A1 agonist piperine shortened the laryngeal vestibule closure time, thereby reducing the prevalence of penetrations and aspirations. Capsaicin additionally improved the efficacy of swallow. Finally, transcutaneous electrical stimulation applied at sensory intensity, without causing muscle contraction, shortened the laryngeal vestibule closure time, thus improving the safety of swallow ; at motor intensity, the safety of swallow was also improved and, in addition, oropharyngeal residue was reduced. The studies of this thesis confirm that is possible to diagnose and to treat dysphagic patients efficiently. They open a new line of research that aims to change the approach of dysphagia therapy from compensation to functional recovery.

Abreviaturas

Abreviaturas AE efectos adversos (adverse events)

OD oropharyngeal dysphagia ( = DO)

AP neumonía por aspiración (aspiration

PAS escala de penetración-aspiración

pneumonia)

(penetration-aspiration scale)

AUC área bajo la curva (area under curve)

PEG gastrostomía endoscópica percutánea

C cierre (closure)

(percutaneous endoscopic gastrostomy)

CAP neumonía adquirida en la comunidad

PPV valor predictivo positivo (positive predictive

(community acquired pneumonia)

value)

CI intérvalos de confianza (confidence intervals)

ROC Receiver Operating Characteristic

COPD enfermedad pulmonar obstructiva crónica

rTMS estimulación magnética transcraneal

(chronic obstructive pulmonary disease)

repetitiva (repetitive transcraneal magnetic

DO disfagia orofaríngea ( = OD)

stimulation)

DSG dorsal swallowing group

RTUC Resource ThickenUp Clear

EAT-10 eating assessment tool-10

SLN nervio superior laríngeo (superior laryngeal

EST extrem spoon thick

nerve)

e-stim electroestimulación (electrostimulation)

SSQ Sydney swallowing questionnaire

FEES fibroendoscópia de la deglución (fiberoptic

tDCS estimulación transcraneal directa

endoscopic evaluation of swallwoing)

(transcraneal direct current stimulation)

FEP pacientes ancianos frágiles (frail elderly

TMS estimulación magnética transcraneal

patients)

(transcraneal magnetic stimulation)

GPJ unión glosopalatina (glossopalatal junction)

TOR-BSST Toronto Bedside Swallowing

GPNph rama faríngea del nervio glosofaríngeo

Screening Test

(glossopharyngeal nerve, pharyngeal branch)

TRP transient receptor potential cation channel

HV voluntarios sanos (healthy volunteers)

TRPA1 transient receptor potential cation

ICD International Statistical Classification of

channel, subfamily A, member 1

Diseases and Related Health Problems

TRPM8 transient receptor potential cation

LV vestíbulo laríngeo (laryngeal vestibule)

channel, subfamily M, member 8

MECV-V método de exploración clínica volumen

TRPV1 transient receptor potential cation

viscosidad ( = V-VST)

channel, subfamily V, member 1

MNA Mini Nutricional Assessment

UES esfínter esofágico superior (upper

MNA-SF Mini Nutricional Assessment short form

esophageal sphincter)

NMES estimulación eléctrica neuromuscular

VFS videofluoroscopia (videofluoroscopy)

(neuromuscular electrical stimulation)

VPJ unión velofaríngea (velopharyngeal junction)

NPV valor predictivo negativo (negative predictive

VSG ventral swallowing group

value)

V-VST volume viscosity swallow test ( = MECV-V)

NTS núcleo del tracto solitario (nucleus tractus

WHO Organización Mundial de la Salud (World

solitarii)

Health Organization)

O apertura (opening)

Índice_________________________________________________________________________

ÍNDICE INTRODUCCIÓN ................................................................................................................. 1 1. Introducción ................................................................................................................. 1 2. Anatomía del sistema deglutorio ................................................................................ 1 2.1 Cavidad oral y lengua ............................................................................................................ 1 2.2 Faringe .................................................................................................................................. 3 2.3 Laringe .................................................................................................................................. 4 2.4 Esfínter esofágico superior ................................................................................................... 7

3. Fisiología de la deglución ............................................................................................ 7 3.1 Fase oral preparatoria ........................................................................................................... 7 3.1 Fase oral propulsora .............................................................................................................. 7 3.1 Fase faríngea ........................................................................................................................ 7 3.1 Fase esofágica ...................................................................................................................... 9

4. Control neural de la deglución ................................................................................... 9 4.1 Estímulo sensorial e innervación aferente ............................................................................ 9 4.2 Sistema nervioso central ......................................................................................................11 4.2.1 Centro deglutorio ...........................................................................................................................11 4.2.2 Estructuras corticales y sub-corticales ..........................................................................................12

4.3 Innervación motora y músculos efectores .............................................................................12

5. Disfagia orofaríngea .................................................................................................... 13 5.1 Epidemiología .......................................................................................................................13 5.2 Fisiopatología .......................................................................................................................16 5.2.1 La disfagia en el paciente anciano ................................................................................................16 5.2.2 La disfagia después de un ictus ....................................................................................................16 5.2.3 La disfagia en las enfermedades neurodegenerativas .................................................................17

6. Diagnóstico .................................................................................................................. 17 6.1 Identificación del paciente vulnerable: cribado ......................................................................17 6.2 Exploración clínica ................................................................................................................18 6.3 Técnicas instrumentales .......................................................................................................20 6.3.1 Videofluoroscopia ..........................................................................................................................20 6.3.2 Fibroendoscopia de la deglución (FEES) .....................................................................................21 6.3.3 Manometría faringoesofágica de alta resolución ..........................................................................21

7. Tratamiento .................................................................................................................. 21 7.1 Medidas higiénico-dietéticas .................................................................................................22

Índice 7.2 Estrategias compensatorias..................................................................................................22 7.2.1 Adaptación de la dieta......................................................................................................22 7.2.1.1 Adaptación de los sólidos .....................................................................................22 7.2.1.2 Adaptación de los líquidos ....................................................................................23 7.2.2 Estrategias posturales......................................................................................................24 7.2.3 Maniobras deglutorias ......................................................................................................24

7.3 Estrategias rehabilitadoras ...................................................................................................24 7.3.1 Praxias neuromusculares .................................................................................................24 7.3.2 Estimulación eléctrica neuro-muscular ...............................................................................24

7.4 Tratamientos quirúrgicos ......................................................................................................25 7.5 Estrategias de neuro-estimulación ........................................................................................25 7.5.1 Estrategias de estimulación sensorial periféricas ................................................................25 7.5.1.1 Estímulos químicos ..............................................................................................25 7.5.1.2 Estímulos eléctricos .............................................................................................26 7.5.2 Estrategias de estimulación central....................................................................................26

8. Complicaciones ........................................................................................................... 26 8.2 Neumonía por aspiración ......................................................................................................27 8.1 Malnutrición ..........................................................................................................................27

Referencias ...................................................................................................................... 28 HIPÓTESIS Y OBJETIVOS ............................................................................................... 35 CAPÍTULO 1. Sensitivity and specificity of the Eating Assessment Tool and the VolumeViscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia ........................ 39 Abstract ......................................................................................................................................41 Introduction ................................................................................................................................41 Materials and Methods ...............................................................................................................42 Subjects .................................................................................................................................42 Design ..................................................................................................................................42 Index tests .............................................................................................................................43 Reference test ........................................................................................................................43 Bolus viscosities ......................................................................................................................43 Post-test probabilities ..............................................................................................................44 Data analysis and statistical methods.........................................................................................44

Results .......................................................................................................................................45 Subjects .................................................................................................................................45

Índice_________________________________________________________________________ Reference test results ..............................................................................................................46 Index test results .....................................................................................................................46 Diagnostic accuracy of the EAT-10 and V-VST ...........................................................................47 Post-test probabilities ..............................................................................................................47 Inter-rater correlation for V-VST ................................................................................................47

Discussion ..................................................................................................................................47 References .................................................................................................................................51

CAPÍTULO 2. Pathophysiology of oropharyngeal dysphagia in the frail elderly ................ 55 Abstract ......................................................................................................................................57 Introduction ................................................................................................................................57 Materials and Methods ...............................................................................................................58 Sample ..................................................................................................................................58 Experimental Design ................................................................................................................58 Videofluoroscopic signs ............................................................................................................59 Oropharyngeal swallow response ..............................................................................................59 Data analysis and statistical methods.........................................................................................60

Results .......................................................................................................................................60 Demographics and clinical inventory scores ................................................................................60 Videofluoroscopic signs of oropharyngeal dysphagia ...................................................................60 Oropharyngeal physiology ........................................................................................................62

Discussion ..................................................................................................................................64 References .................................................................................................................................66

CAPÍTULO 3. Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly ...................................................................................................................... 69 Abstract ......................................................................................................................................71 Introduction ................................................................................................................................71 Materials and Methods ...............................................................................................................72 Case-control study ...................................................................................................................72 Pathophysiological study ..........................................................................................................72 Statistical analysis ...................................................................................................................72

Results .......................................................................................................................................73 Case-control study ...................................................................................................................73 Pathophysiological study ..........................................................................................................74

Índice Discussion ..................................................................................................................................75 References .................................................................................................................................77

CAPÍTULO 4. The effects of a xanthan gum-based thickener on the swallowing function of patients with dysphagia...................................................................................................... 81 Abstract ......................................................................................................................................83 Introduction ................................................................................................................................83 Materials and Methods ...............................................................................................................84 Study population .....................................................................................................................84 Experimental design ................................................................................................................84 Clinical test .............................................................................................................................84 Videofluoroscopy ....................................................................................................................85 Bolus rheology .......................................................................................................................85 Product safety ........................................................................................................................86 Data analysis and statistical methods ........................................................................................86

Results .......................................................................................................................................86 Study population .....................................................................................................................86 Effect of RTUC on clinical signs and symptoms of OD .................................................................87 Effect of RTUC on videofluoroscopic signs of OD .......................................................................88 Effect of RTUC on oropharyngeal physiology ..............................................................................89 Product safety .........................................................................................................................89

Discussion ..................................................................................................................................90 References .................................................................................................................................92

CAPÍTULO 5. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia ................................................................................................... 95 Abstract ......................................................................................................................................97 Introduction ................................................................................................................................97 Materials and Methods ...............................................................................................................98 Patients ..................................................................................................................................98 Videofluoroscopic procedures ...................................................................................................98 Drugs .....................................................................................................................................99 Videofluoroscopic signs ............................................................................................................99 Oropharyngeal swallow response ..............................................................................................99 Statistical methods ..................................................................................................................99

Índice_________________________________________________________________________ Results ..................................................................................................................................... 100 Patient demographics and clinical assessment of OD ................................................................ 100 Acceptability of the boluses .................................................................................................... 100 Effect of capsaicinioids on videofluoroscopic signs of efficacy and safety of swallow...................... 101 Effect of capsaicinoids on oropharyngeal swallow response ....................................................... 101 Stroke patients ...................................................................................................................... 102

Discussion ................................................................................................................................ 104 References ............................................................................................................................... 105

CAPÍTULO 6. Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia ................................................................................................. 109 Abstract .................................................................................................................................... 111 Introduction .............................................................................................................................. 111 Materials and Methods ............................................................................................................. 112 Study population ................................................................................................................... 112 Study design ......................................................................................................................... 112 Data analysis ........................................................................................................................ 113 Adverse events ..................................................................................................................... 113 Statistical methods ............................................................................................................... 113

Results ..................................................................................................................................... 113 Baseline characteristics .......................................................................................................... 113 Effect of piperine on videofluoroscopic signs of impaired safety and efficacy of swallow ................. 113 Effect of piperine on the physiology of impaired swallow response .............................................. 114 Adverse events ..................................................................................................................... 115

Discussion ................................................................................................................................ 116 References ............................................................................................................................... 117

CAPÍTULO 7. Effect of surface sensory and motor electrical stimulation on chronic poststroke oropharyngeal dysfunction ............................................................................. 121 Abstract .................................................................................................................................... 123 Introduction .............................................................................................................................. 123 Materials and Methods ............................................................................................................. 124 Patients ................................................................................................................................ 124 Study design ......................................................................................................................... 124 Videofluoroscopic procedures ................................................................................................. 125

Índice Efficacy measurements .......................................................................................................... 125 Adverse events ..................................................................................................................... 125 Statistical analysis ................................................................................................................. 125

Results ..................................................................................................................................... 126 Patient characteristics ............................................................................................................ 126 Effect of treatments ............................................................................................................... 127 Adverse events ..................................................................................................................... 128

Discussion ................................................................................................................................ 129 References ............................................................................................................................... 131

DISCUSIÓN GENERAL .................................................................................................. 135 CONCLUSIONES ............................................................................................................ 157 ANEXO 1 ......................................................................................................................... 161 ANEXO 2 ......................................................................................................................... 165

INTRODUCCIÓN

Introducción

Introducción mecanismos compensatorios, para los pacientes con disfagia. Estos aspectos son los que se han

1. INTRODUCCIÓN

pretendido abordar, de forma integrada, durante el desarrollo de esta Tesis Doctoral.

La deglución es el proceso fisiológico mediante el

2. ANATOMÍA DEL SISTEMA DEGLUTORIO

cual se transportan sólidos y líquidos desde la boca hasta el estómago. Es un proceso rápido y complejo que requiere de la contracción y relajación

2.1 Cavidad oral y lengua

coordinada de más de 30 pares de músculos de la

La cavidad oral es la primera porción del tubo

boca, faringe, laringe y esófago, así como la

digestivo.

coordinación entre el sistema digestivo y el sistema respiratorio.

Múltiples

enfermedades

y

boca y otra central, o cavidad bucal propiamente dicha. Ambas partes se comunican entre sí por los

como disfagia. Dependiendo de su localización, la orofaríngea

espacios interdentales y el espacio retrodentario,

o

situado entre los últimos molares y la rama

esofágica. La disfagia orofaríngea, objetivo de

ascendente del maxilar inferior. El vestíbulo bucal

estudio de esta Tesis Doctoral, es un trastorno

es el espacio situado entre los labios y las mejillas y

prevalente en la población anciana y en pacientes

los arcos gingivodentarios. Se abre al exterior por

con enfermedades neurológicas, que se asocia a

medio del orificio bucal que está formado por los

graves complicaciones nutricionales y respiratorias, con

una

alta

mortalidad

asociada.

de

gingivodentarios: una periférica o vestíbulo de la

de forma segura y eficaz, síntoma que se conoce en

procesos

anatómico dividido en dos partes por los arcos

molestias para formar o mover el bolo alimentario

clasificarse

los

articulación y resonancia del habla. Es un espacio

conduciendo a la aparición de dificultades o

puede

en

masticación, degustación, insalivación, deglución,

co-

morbilidades pueden alterar esta función fisiológica,

disfagia

Interviene

labios superior e inferior cuya unión forman el

Está

sello labial.

específicamente reconocida por la Organización Mundial de la Salud (WHO) en la International

La cavidad bucal está limitada hacia delante y

Statistical Classification of Diseases and Related

hacia los lados por los arcos gingivodentarios, por

Health Problems (ICD-9 y ICD-10) como un

arriba por la bóveda palatina y por abajo por el

trastorno que afecta al sistema digestivo, recibiendo

suelo de la boca. Hacia atrás, se comunica con la

para su diagnóstico los códigos 787.2 y R13.1,

faringe por el istmo de las fauces, un orificio

respectivamente.

circunscrito por el velo del paladar, la úvula, los

orofaríngea

es

A pesar de esto, la disfagia un

trastorno

poco

pilares anteriores del velo y la base de la lengua.

conocido,

infradiagnosticado e infratratado. Por este motivo,

En la bóveda palatina se pueden distinguir dos

pensamos que es importante profundizar en el

partes: los dos tercios anteriores se denominan

conocimiento de las alteraciones de la deglución y

paladar duro y el tercio posterior, paladar blando. El

las complicaciones que conllevan así como mejorar

paladar duro está formado por tres capas, la capa

las herramientas diagnósticas y en especial, abrir

ósea formada por las apófisis palatinas de los

las puertas a nuevas alternativas de tratamiento,

maxilares y las láminas horizontales de los huesos

hasta

palatinos, la capa mucosa y la capa glandular. El

el

momento

escasas

y

centradas

en

-1-

Introducción

___________________________________________

paladar blando es un tabique músculo-membranoso

la cavidad bucal en reposo. La mucosa del dorso

que prolonga la bóveda palatina hacia atrás y

de la lengua, la parte superior, está provista de las

abajo, y separa la nasofaringe de la orofaringe. El

papilas linguales que contienen receptores para el

borde posterior del paladar blando presenta en su

gusto: las filiformes, delgadas y puntiagudas, son

parte media una prolongación de 10 a 15 mm de

las más abundantes. Entre ellas se encuentran

longitud, la úvula, y a cada lado, dos repliegues

dispersas las papilas fungiformes y delante del

curvilíneos, uno anterior y otro posterior, llamados

surco terminal hay una hilera de 8 a 12 papilas más

pilares anteriores y posteriores del velo del paladar

grandes, llamadas circunvaladas o caliciformes. En

o

ambos bordes laterales de la lengua encontramos

arcos

palatogloso

y

palatofaríngeo

las papilas foliadas [1] (Figura 2).

respectivamente. El suelo de la boca está delimitado por el espacio situado entre la mandíbula y el hueso hioides, y contiene principalmente músculos. Los músculos milohioideos constituyen la pared inferior de este espacio. Sus fibras posteriores se insertan en el hueso hioides y desde aquí se dirigen hacia delante y se insertan en el arco mandibular. Entre la piel y los milohioideos, a cada lado de la línea media se sitúa el vientre anterior del músculo digástrico que va desde la cara interna del mentón hasta el hioides. Durante la deglución, este músculo y el milohioideo traccionan del hioides hacia delante y lo elevan y además abren la boca. Superiormente a los milohioideos, el suelo de la boca está reforzado por el músculo geniohioideo, que se extiende desde la cara interna del mentón hasta el hioides (Figura 1). La lengua ocupa la parte media del suelo de la boca. Es un órgano muy móvil formado por músculo estriado recubierto de mucosa. En la lengua se

diferencian

dos partes principales

divididas por un surco en forma de V abierta hacia delante, llamada surco terminal o V lingual: la posterior o faríngea, la raíz, y la anterior o bucal, el cuerpo. La parte faríngea de la lengua, parte fija, ancha y gruesa, constituye la pared anterior de la orofarínge y se une al paladar blando por los arcos palatoglosos y a la epiglotis, por los pliegues

Figura 1: Músculos suprahioideos, vista lateral (A) y vista inferior (B). Reproducido de: Drake RL et al (2005) [2].

glosoepiglóticos, formando la vallécula. La parte oral de la lengua, el cuerpo, ocupa casi totalmente -2-

Introducción

Figura 2: Sección sagital (A) y vista superior (B) de la lengua. Reproducido de: Drake RL et al (2005) [2]. velofaríngeo, que cerrará la comunicación entre

2.2 Faringe

la nasofaringe y la orofaringe y evitará la

La faringe es la segunda porción del tubo digestivo.

regurgitación de alimentos a la cavidad nasal.

Es un conducto músculo-membranoso situado detrás de las fosas nasales y de la boca y que

La orofaringe se extiende desde el istmo faríngeo

termina, por abajo, en la laringe y la tráquea por

hasta el plano delimitado por el hueso hioides o

una parte, y en el esófago por la otra. Es un

punto de inserción de la epiglotis. Se comunica con

conducto mixto desde el punto de vista fisiológico,

la cavidad oral por la parte anterior, por medio del

pues forma parte tanto de la vía digestiva como de

istmo de las fauces. Por esta parte de la faringe

la vía respiratoria. Basándose en las aberturas que

pasan los alimentos y el aire respiratorio. Los

se hallan en la parte anterior de la faringe, este

alimentos son conducidos de la boca a la parte

órgano se divide en tres porciones anatómicas

inferior de la faringe por los canales alimentarios

nasofaringe,

que encontramos a cada lado del tercio posterior de

craneocaudales:

orofaringe

y

laringofaringe (Figura 3).

la lengua.

La nasofaringe desempeña una función puramente

La laringofaringe se extiende desde el hueso

respiratoria y fonatoria. Se extiende desde la base

hioides hasta el borde inferior del cartílago

del cráneo, por detrás de las fosas nasales (con las

cricoides, a la altura de la sexta vértebra cervical,

que comunica a través de las coanas) hasta el velo

donde empieza el esófago. Se localiza detrás de la

del paladar, donde se comunica con la orofaringe

laringe y tiene forma de embudo, estrechándose en

por un espacio estrecho, denominado istmo de la

la parte inferior en dirección al esfínter esofágico

faringe. En el proceso de la deglución el velo del

superior. La pared anterior corresponde al orificio

paladar se eleva y se pone en contacto con la

laríngeo. Este orificio, de forma elíptica, tiene los

pared posterior de la faringe formando el sello

límites formados por los bordes de la epiglotis, los pliegues ariepiglóticos.

-3-

Introducción____________________________________________________________________

Figura 3: Vista lateral (A), posterior (B) y superior (C) de la faringe. Reproducido de: Drake RL et al (2005) [2]. Caudalmente

al

abertura,

función

la

plano de

delimitado la

por

dicha

laringofaringe

elevadores

de

cada

lado.

Los

músculos

es

constrictores o intrínsecos (músculo constrictor

exclusivamente el paso de los alimentos. Por

superior, el medio y el inferior) están formados por

debajo del pliegue ariepiglótico se encuentran los

fibras transversales y oblicuas y su función es la de

senos piriformes, continuación de los canales

estrechar la faringe al paso del bolo alimentario con

alimentarios, que facilitan el paso del alimento

un movimiento peristáltico (Figura 4). Los músculos

hacia el esófago.

elevadores o extrínsecos tienen la función de elevar y acortar la faringe durante la deglución y son el

Histológicamente, la faringe está constituida por

palatofaríngeo,

tres capas: la mucosa o túnica interna, en la cara

el

estilofaríngeo

y

el

salpingofaríngeo [3].

interior, un armazón fibroso interpuesto entre la túnica muscular y la mucosa, llamado fascia

2.3 Laringe

faringobasilar o túnica media y los músculos de la túnica externa. La pared muscular de la faringe está

La laringe forma parte de la vía aérea y es también

constituida por diez músculos estriados bilaterales:

el órgano de la fonación. Está situada en la parte

tres

mediana y anterior del cuello, debajo del plano del

músculos

constrictores

y

dos

músculos -4-

Introducción

Figura 4: Músculos constrictores de la faringe. Vista lateral (A) y posterior (B). Reproducido de: Drake RL et al (2005) [2]. hueso hioides y de la lengua y delante de la faringe,

adelante y la epiglotis se dobla posteriormente

con la cual comunica cranealmente y por encima de

como resultado de la presión pasiva de la base de

la tráquea con la cual comunica caudalmente. La

la lengua y la contracción activa del músculo

laringe

ariepiglótico.

está

constituida

por

un

esqueleto

Mediante

este

movimiento,

la

cartilaginoso, las articulaciones y ligamentos que

epiglotis cumple su función principal que es

unen los cartílagos, los músculos que los movilizan

proteger la vía respiratoria y desviar los

y la mucosa que tapiza el interior del órgano. Los

alimentos y los líquidos de la entrada de la

principales cartílagos que forman la laringe son: el

laringe hacia los senos piriformes y la hipofaringe.

tiroides, el más voluminoso, es la pieza principal

Los músculos de la laringe pueden dividirse entre

de la laringe; el cricoides, situado debajo del

extrínsecos (aquellos que unen la laringe con los

tiroides, sobre él se apoya toda la laringe, precede

órganos vecinos) e intrínsecos (aquellos que toman

inmediatamente a la tráquea; los aritenoides son

sus

dos, se sitúan a ambos lados de la línea media y

inserciones

en

los

cartílagos

laríngeos

asegurando su movilidad). Dentro de los músculos

reposan sobre el borde superior del cricoides; la

extrínsecos encontramos los elevadores de la

epiglotis, de naturaleza elástica y de forma

laringe: tirohioideo, estilofaríngeo, palatofaríngeo,

ovalada, se fija al cartílago tiroides por el ligamento

milohioideo, geniohioideo y estilohioideo; y los

tiro-epiglótico de su extremo inferior, y tiene el

depresores

borde superior libre que se sitúa por detrás de la

de

la

esternohioideo

lengua y del hioides sobresaliendo por encima de

y

laringe:

esternotirohioideo,

omohioideo.

Los

músculos

intrínsecos pueden dividirse en tres grupos, de

éste. La cara anterior o lingual de la epiglotis está

acuerdo

tapizada por mucosa lingual que forma tres

con

sus

acciones

principales:

los

cricoaritdenoideos posteriores y laterales y los

pliegues gloso-epiglóticos los cuales delimitan

aritenoides oblicuos y transverso modifican las

dos fosas, las valléculas. Durante la deglución, el

dimensiones

hueso hioides se mueve hacia arriba y hacia

de

la

glotis.

Los

cricotiroideos,

cricoaritenoideos posteriores, tiroaritenoideos -5-

y

Introducción____________________________________________________________________ vocalis regulan la tensión de los ligamentos

pliegues vestibulares o falsas cuerdas vocales y

vocales.

los

está limitado en su pared anterior por la cara

ariepiglóticos actúan facilitando el cierre de la

posterior de la epiglotis; el segmento medio lo

laringe, aduciendo los pliegues ariepiglóticos y

forma el ventrículo laríngeo, limitado en su parte

aproximando los cartílagos aritenoides a la base de

superior por los pliegues vestibulares y en su parte

la epiglotis y los tiroepiglóticos facilitan la apertura

inferior por los pliegues vocales o cuerdas vocales

de la laringe por su acción sobre los pliegues

verdaderas. El espacio comprendido entre los

ariepiglóticos.

pliegues vocales cuando están abiertos es la

Los

aritenoideos

oblicuos

y

hendidura glótica; la cavidad infraglótica es el

Internamente se puede dividir la laringe en tres

segmento inferior de la laringe, limitado arriba por

niveles: el vestíbulo laríngeo (segmento superior)

los pliegues vocales y abajo por la tráquea [4]

conforma la entrada de la laringe y termina en los

(Figura 5).

Figura 5: Vista lateral-posterior (A), sección coronal (B) y vista superior (C) de la cavidad laríngea. Vista superior de la laringe obtenida mediante fibro-laringoscopio (D). Reproducido de: Drake RL et al (2005) [2].

-6-

Introducción 2.4 Esfínter esofágico superior

estructuras óseas que rodean la cavidad oral y mezclándolos con los elementos líquidos del bolo

El esfínter esofágico superior (UES) es la zona de

ingerido. La saliva secretada también facilita la

alta presión del tracto digestivo superior que separa

disolución y la lubricación del bolo sólido y

el esófago y la faringe. El UES se encuentra

contribuye al inicio del proceso químico de

cerrado tónicamente de forma que previene la

digestión por medio de la enzima α-amilasa, que

entrada de aire al tracto digestivo y el reflujo de

cataliza la ruptura del almidón en maltosas,

material del esófago a la faringe. En cambio, el

maltotriosas y dextrinas. Una vez el bolo está

UES se abre en respuesta a una deglución,

preparado adecuadamente, es posicionado en un

permitiendo el paso del bolo alimentario al esófago

receso de la parte posterior del dorso de la lengua

y permite también la salida de material del esófago

para ser propulsado hacia la orofaringe [7].

durante el vómito o los eructos. Se encuentra a la altura de la 5ª-6ª vértebra cervical y mide entre 2 y

3.2 Fase oral propulsora

4 cm de longitud. Está formado por el músculo parte

Es también voluntaria y se caracteriza por la

inferior del músculo constrictor faríngeo y la parte

propulsión del bolo alimentario hacia la orofaringe

superior del esófago cervical [5;6].

por parte de la lengua. Al inicio de la fase oral

cricofaríngeo

(componente

principal),

la

propulsora, la parte anterior de la lengua se pone en contacto con el paladar duro ubicando el bolo en

3. FISIOLOGÍA DE LA DEGLUCIÓN

la parte posterior de la cavidad oral. A su vez, la parte posterior de la lengua está en contacto

La deglución se divide en cuatro grandes fases,

con el paladar blando, formando el sello

cada una de las cuales (frecuentemente más de

glosopalatino y evitando la caída prematura del

una) puede estar afectada y originar un trastorno

bolo hacia la faringe. Al iniciar la propulsión, la

deglutorio.

lengua presiona contra el paladar duro generando una onda de presión en dirección antero-posterior

3.1 Fase oral preparatoria

que propulsa el bolo hacia la orofaringe al mismo

Es de control voluntario y su objetivo es la ingesta,

tiempo que el paladar blando se eleva para abrir el

masticación y la formación del bolo alimentario. La

sello glosopalatino y cerrar la nasofaringe. La fase

ingesta del bolo alimentario requiere el descenso

oral se puede considerar finalizada cuando la cola

de la mandíbula, la apertura de los labios y la

del bolo entra en la orofaringe, momento en el que

depresión de la lengua, acciones que aumentan el

la parte posterior del dorso de la lengua vuelve a

volumen de la cavidad oral para acomodar el bolo

cerrar el sello glosopalatino con el paladar blando

ingerido. La masticación es un proceso necesario

para prevenir el escape retrógrado del bolo hacia la

para adecuar el tamaño, la forma y la consistencia

cavidad oral [7].

del bolo ingerido. Esta acción requiere un complejo

3.3 Fase faríngea

y repetitivo movimiento mandibular y el molido de sólidos con los dientes, que son posicionados sobre

Es involuntaria y comprende el período desde que

sus superficies con la ayuda de las mejillas y la

la cabeza del bolo entra en la cavidad faríngea

lengua. La lengua también ayuda a reducir los

hasta que la cola del bolo sale del esfínter

sólidos blandos o solubles aplastándolos contra las

esofágico superior y este se cierra. Habitualmente

-7-

Introducción____________________________________________________________________ la fase faríngea se produce como continuación de

que

cierra

la

nasofaringe

para

evitar

la

la fase oral, sin embargo, la fase faríngea se puede

regurgitación nasal del bolo. Seguidamente, y a

activar sin necesidad de la fase oral en respuesta a

medida que el bolo va avanzando por la faringe se

estímulos faríngeos.

producen una serie de acontecimientos destinados a proteger la vía respiratoria: por un lado, se

La fase faríngea comprende la respuesta motora

produce la adducción de las cuerdas vocales y de

oro-faríngea, la cual se caracteriza por una serie

los aritenoides que sellan la vía respiratoria; los

de acontecimientos que permiten pasar de una

aritenoides, además, se mueven hasta contactar la

configuración respiratoria (aquella en la cual la

base de la epiglotis y se produce la retroflexión de

nasofaringe, la orofaringe, la laringe y el resto de la

la epiglotis como consecuencia de la presión pasiva

vía respiratoria forman un canal continuo por el que

por parte de la base de la lengua y la contracción

circula el flujo de aire) a una de digestiva (que

activa de los músculos ariepiglóticos, que acaba de

comunica la boca, la orofaringe, la laringofaringe y

cerrar el vestíbulo laríngeo y desvía el bolo

el esófago), mantener la configuración digestiva

alimentario fuera de la entrada de la laringe. Por

durante el tránsito del bolo alimentario por la

otro lado, los músculos suprahioideos y los

faringe y finalmente volver a la configuración

músculos longitudinales de la laringe, mueven el

respiratoria. El tránsito entre estas configuraciones

hioides y la laringe hacia arriba y anteriormente, de

se produce gracias a la apertura y al cierre

forma que posicionan la entrada de la laringe bajo

coordinado del sello glosopalatino, el sello velo-

la base de la lengua, fuera de la zona de paso del

faríngeo, el vestíbulo laríngeo y el UES [8;9].

bolo alimentario. Esta acción ayuda también al

Inmediatamente después de la apertura del cierre

acortamiento y expansión del espacio hipofaríngeo

glosopalatino y por tanto de la entrada del bolo en

y a la abertura del UES, que a su vez también se

la orofaringe, el paladar blando se eleva y la pared

eleva unos 2 - 2,5 centímetros, facilitando el paso

posterior de la faringe se mueve medialmente para

del bolo hacia el esófago [10] (Figura 6).

entrar en contacto y formar el sello velo-faríngeo

Figura 6: Vistas laterales de la cabeza y el cuello mostrando la progresión del bolo por la cavidad oral y la faringe. Adaptado de: Logemann JA (2010) [11].

-8-

Introducción

4. CONTROL DEGLUCIÓN

La contracción secuencial de los tres músculos constrictores faríngeos se ha postulado como la

NEURAL

DE

LA

fuerza motriz que impulsa el bolo hacia el esófago. Sin embargo, la evidencia de que la cabeza del

El control neural de la deglución se puede definir

bolo se mueve más rápido que la onda de

cómo una red multidimensional en la que diferentes

contracción faríngea sugiere que la energía cinética

niveles del sistema nervioso están involucrados y

aplicada al bolo al ser propulsado de la boca a la

conectados. Intervienen los receptores periféricos

orofaringe por la lengua es suficiente para llevarlo a

que integran la información sensorial relacionada

través de la faringe, mientras que los constrictores

con las características del bolo, los nervios

faríngeos podrían tener la principal función de

aferentes que transmiten esta información a los

realizar un efecto de barrido y aclaramiento del bolo

centros deglutorios del bulbo raquídeo y a las

[12;13]. Se ha evaluado la sincronización de los

regiones corticales y sub-corticales, que integran y

principales parámetros de la respuesta motora

modulan la respuesta motora, que es transmitida a

orofaríngea y se ha puesto de manifiesto que en

los

individuos jóvenes y sanos el cierre del vestíbulo

motoneuronas de diversos pares craneales (Figura

laríngeo (tomando como tiempo 0 la apertura del

8).

músculos

efectores

por

parte

de

las

sello glosopalatino) se produce antes de los 160 ms, la apertura del UES se produce antes de los 200 ms y la duración total de la deglución es inferior a 750 ms [8].

3.4 Fase esofágica Se inicia con la apertura del UES y continúa con la peristalsis esofágica. En la apertura del UES intervienen cuatro mecanismos principales: a) la interrupción del tono vagal sobre el músculo cricofaríngeo, lo que permite la desaparición de la contracción muscular de origen central que lo mantiene cerrado; b) la tracción sobre la cara anterior del esfínter causada por la contracción de

Figura 8: Esquema de la red multidimensional implicada en el control neural de la deglución.

la musculatura supra-hioidea; c) la presión sobre el

4.1

esfínter ejercida por el bolo alimentario, la magnitud

aferente

de la cual depende de la fuerza de propulsión

Estímulo

sensorial

e

innervación

lingual, y d) la distensibilidad del esfínter que

El estímulo sensorial es un elemento crítico en la

permite su relajación completa, con bajas presiones

deglución [14]. El feedback sensorial durante la

residuales y escasa resistencia durante el paso del

fase oral permite el adecuado posicionamiento de

bolo [5].

las

estructuras

orales

y

la

preparación

y

posicionamiento del bolo para su transporte, así como

modula

la

fuerza,

la

velocidad

y

la

coordinación de las contracciones musculares.

-9-

Introducción____________________________________________________________________ Facilita también el inicio de la respuesta motora

nervios

orofaríngea, que no es fija ni refleja como se había

sensorial al bulbo olfatorio.

postulado históricamente (por lo que no es adecuado usar el término reflejo deglutorio), sino que también depende de este feedback sensorial y puede adaptarse a diferentes características del bolo [15]. El sistema sensorial que integra la información del bolo alimentario es complejo y está formado por tres tipos de estímulos fundamentales: el gusto, el olor y la quimiosensación.

olfatorios

transmitirán

la

información

Por otro lado, además de los receptores del gusto y del olor, existen estímulos químicos, térmicos y mecánicos que actúan a través de receptores iónicos que se encuentran en las membranas de las neuronas sensoriales primarias y las células epiteliales orofaríngeas, que también son capaces de evocar respuestas sensoriales. A este proceso se la llama somatosensación, y en concreto la

La señalización del gusto se realiza a través de las

integración

papilas gustativas, que pueden distinguir 5 gustos

quimiosensación. El nervio trigémino (V par

fundamentales: el dulce, el salado, el amargo, el

craneal)

ácido y el umami. Las sales y los ácidos son

quimiosensación,

detectados por canales iónicos (ionotrópicos),

glosofaríngeo y el nervio vago [17]. Estas fibras,

localizados en la membrana apical de las células

y más en concreto la rama maxilar del trigémino, la

Tipo III de las papilas gustativas, mientras que las

rama faríngea del glosofaríngeo y dos ramas del

sustancias que producen un sabor amargo, dulce o

nervio vago, el nervio superior laríngeo y la rama

umami (como por ejemplo el glutamato) activan

faríngea, inervan las áreas más efectivas para

receptores metabotrópicos (acoplados a proteína

disparar la respuesta motora orofaríngea, como son

G) de las células Tipo II de las papilas gustativas.

el arco palatofaríngeo y los pliegues ariepiglóticos

Las células gustativas de los dos tercios anteriores

[18]. Estas aferencias, que proyectan hacia el

de la lengua se encuentran en las papilas

centro de la deglución en el tronco cerebral y a

fungiformes, que son inervadas por la rama cuerda

estructuras corticales y sub-corticales, expresan las

del tímpano del nervio facial (VII par craneal),

principales dianas moleculares encargadas de

mientras que en el tercio posterior de la lengua, se

integrar los estímulos somatosensoriales, que son

encuentran en las papilas circunvaladas y foliadas,

la familia de receptores-canales transmembrana

que están inervadas principalmente por el nervio

Transient Receptor Potencial Ion Channel (TRP)

glosofaríngeo

células

[19], y más en concreto los subtipos TRPV1,

gustativas del paladar blando están inervadas por

TRPA1 y TRPM8. Son agonistas de estos canales,

otra rama del nervio lingual, el nervio petroso

actuando como estímulos somatosensoriales, la

superficial mayor, y las de la epiglotis y la laringe

capsaicina y las temperaturas elevadas (agonistas

están inervadas por el nervio superior laríngeo, una

TRPV1) [20], la piperina (agonista TRPV1 y

rama del nervio vago (X par craneal) [16].

TRPA1) [21], el mentol (agonista TRPM8) [22;23] y

(IX

par

craneal).

Las

En el proceso de la ingesta, se pueden liberar moléculas volátiles en la parte trasera de la cavidad bucal, que a través de la nasofaringe pueden producir la estimulación retronasal del epitelio olfatorio de la parte superior de la cavidad nasal. Estas moléculas actuando en los receptores de los

de

juega

los un

papel

como

estímulos

químicos,

fundamental también

el

en

la

nervio

las temperaturas bajas (agonista TRPA1 y TRPM8) [24]. Una de nuestras hipótesis de trabajo es que la suplemetación del bolo alimentario con estos estímulos podría incrementar el input sensorial y modular el componenete motor de la respuesta motora orofaríngea.

- 10 -

Introducción

Figura 7: Innervación aferente de la cavidad oral y de la faringe. Adaptado de: Netter FH (2014) [25].

4.2 Sistema nervioso central

sináptica de las interneuronas del DSG como consecuencia

4.2.1 Centro deglutorio El centro deglutorio se encuentra en el bulbo raquídeo del tronco encefálico. Consiste en dos hemi-centros, cada uno situado en un lado de la médula, que deben estar bien sincronizados para organizar

la

contracción

coordinada

de

los

músculos bilaterales de la región orofaríngea y del esófago.

Está

interneuronas:

formado el

Dorsal

por

dos

grupos

Swallowing

de

Group

(DSG), localizado en el Núcleo del Tracto Solitario (NTS) y el Ventral Swallowing Group (VSG), localizado en la cara ventrolateral del bulbo, justo por encima del núcleo ambiguo. La respuesta

del

estímulo

de

las

neuronas

sensoriales, ocurre con una latencia muy corta y estable de 1 a 2 ms, indicando que al menos algunas de estas neuronas están conectadas de forma mono-sináptica con las fibras aferentes. Por otro lado, las interneuronas del VSG requieren de varios pulsos para iniciar la respuesta, la latencia de la cual es visiblemente más larga (7-12 ms) y variable, sugiriendo la existencia de una vía polisináptica. Cabe destacar también que se puede iniciar una respuesta en estas neuronas como consecuencia de la estimulación de áreas corticales específicas, con una latencia más corta en las

- 11 -

Introducción____________________________________________________________________ neuronas del DSG (5-8 ms) que en las del VSG

proceso deglutorio es bilateral aunque presenta

(10-16

que

una asimetría inter-hemisférica (independiente de

probablemente las neuronas del VSG son activadas

la mano dominante), siendo uno de los hemisferios

vía neuronas del DSG, siendo las interneuronas del

el

DSG las responsables de integrar la información

consecuencia, el dominante para la deglución [27].

ms).

Estos

resultados

sugieren

convergente de la periferia y de las áreas corticales y generar el patrón motor deglutorio cuando se alcanza el umbral de estímulo necesario, mientras que

las

interneuronas

del

VSG

serían

las

responsables de distribuir la respuesta a los

que

muestra

mayor

activación

y

en

Las estructuras sub-corticales implicadas en la función deglutoria incluyen los ganglios basales, la amígdala, el tálamo y el cerebelo, sin embargo, su función específica en el proceso deglutorio no está del todo clara.

diferentes núcleos motores [26].

4.3 4.2.2 Estructuras corticales y sub-corticales

por

mecanismos

bulbares,

la

corteza cerebral juega un papel fundamental en el inicio voluntario y la regulación de la deglución. Diferentes estudios clínicos, electrofisiológicos y de neuroimagen,

han

determinado

las

motora

y

músculos

efectores

Aunque el control de la deglución está mediado principalmente

Innervación

áreas

cerebrales implicadas en el proceso deglutorio. Las regiones que presentan una mayor activación tanto en la deglución voluntaria como en las degluciones de saliva espontáneas son la circunvolución precentral lateral (que incluye la corteza motora primaria), la circunvolución post-central lateral (que incluye la corteza somatosensorial), la ínsula y la circunvolución frontal inferior - área de Broca(relacionadas con el procesamiento sensorial del

Tal y cómo se ha descrito en los puntos anteriores de

este

capítulo,

muchos

son

los

grupos

musculares que participan en el proceso deglutorio, tanto en la fase oral como en la fase faríngea. Todos ellos son músculos estriados que usan acetilcolina como neurotransmisor vía receptores nicotínicos en la placa motora. El soma de las motoneuronas que inervan estos músculos se encuentra en los núcleos de la protuberancia del tronco encefálico (trigémino y facial), del bulbo raquídeo (núcleo ambiguo e hipogloso) y de la médula espinal cervical (C1-C2). Los axones de estas neuronas viajan a través de los pares craneales V, VII, IX, X, XI y XII y el asa cervical.

estímulo gustatorio y las sensaciones de la boca y

Los músculos del grupo facial (orbicularis orbis y

la faringe), la corteza pre-motora, el precúneo -zona

buccinator) están inervados por el VII par craneal.

media de la corteza parietal superior-, el área

Durante la masticación, su función es sellar la

motora suplementaria y la circunvolución del

cavidad oral y posicionar la comida sobre las

cíngulo anterior (relacionadas con la atención y la

superficies de molido de los dientes. Los músculos

planificación del movimiento deglutorio), y las

masticadores

circunvoluciones temporales transversal, superior y

interno y externo) están inervados por la rama

medial (que parecen estar relacionadas con el

mandibular del V par craneal. Su acción es mover

procesamiento de los sonidos de la deglución, así

la mandíbula durante la masticación, ejerciendo la

como la integración de estímulos gustatorios) [27-

fuerza suficiente par moler la comida. Los músculos

29]. Cabe destacar que en individuos sanos la

de la lengua, tanto los intrínsecos (longitudinal

activación de la red neural implicada en el

superior, transverso y vertical) como los extrínsecos

- 12 -

(masetero,

temporal,

pterigoideo

Introducción (hiogloso, geniogloso y estilogloso) están inervados

viajan a través de la rama inferior laríngea del

por el nervio hipogloso (XII par craneal). Las

nervio recurrente laríngeo (X par craneal) [7].

contracciones de los diferentes músculos linguales permiten la elevación, depresión, protrusión y retracción de la lengua permitiendo por lo tanto, la preparación,

formación,

posicionamiento

5. DISFAGIA OROFARÍNGEA

y

propulsión del bolo alimentario.

5.1 Epidemiología

Los músculos suprahioideos actúan elevando el

La disfagia orofaríngea (DO) es un síntoma que se

hueso hioides y la laringe, mientras que los

refiere a la dificultad o molestia para formar o

músculos infrahioideos realizan la acción contraria.

mover el bolo alimenticio de la boca al esófago. El

Son músculos suprahioideos el digástrico (el vientre

término disfagia proviene del griego “dis” que

anterior inervado por el V par craneal y el vientre

significa “dificultad” y “fagia” que significa “comer”.

posterior inervado por el VII par craneal), el estilohioideo (inervado por el VII par craneal), el geniohioideo (inervado por el XII par craneal) y el milohioideo (inervado por el V par craneal). Los músculos

infrahioideos

(omohioideo,

esternohioideo, tirohioideo y esternotirohioideo)

A pesar de que a menudo se utilizan como términos sinónimos, debemos diferenciar entre disfagia orofaríngea (síntoma) y disfunción deglutoria, que se refiere a la alteración evidenciada en las pruebas instrumentales.

están inervados por el asa cervical. Los músculos

La DO puede originarse por diferentes causas que

del paladar (músculo de la úvula, palatogloso y

se resumen en la Tabla 1. El objetivo de estudio de

elevador del velo del paladar) están inervados por

esta Tesis Doctoral son las alteraciones deglutorias

el plexo faríngeo (constituido por ramas del IX y X

que se asocian a patologías neurológicas en

pares craneales y del ganglio cervical superior)

individuos adultos y al envejecimiento.

mientras que el músculo tensor del velo del paladar

La prevalencia real de DO es difícil de determinar y

lo está por el nervio mandibular (V par craneal).

los estudios publicados difieren significativamente

Estos músculos actúan durante la fase oral de la

en los datos reportados, dependiendo de diferentes

deglución para endurecer el paladar blando, bajar

factores, como pueden ser: la patología asociada,

el velo del paladar para evitar la caída prematura

el estadio de la enfermedad asociada, el método

del bolo en la faringe o elevar el velo del paladar

diagnóstico

para abrir el sello glosopalatino. Los músculos de la

residencia, comunidadN) y el país donde se ha

faringe, tanto los constrictores como los elevadores,

desarrollado el estudio, entre otros. En la Tabla 2

están inervados por el plexo faríngeo del nervio

se describe la prevalencia de disfagia descrita en

vago, a excepción del músculo estilofaríngeo que

ancianos, pacientes que han sufrido un ictus y

está inervado por el IX par craneal. Finalmente,

pacientes con enfermedades neurodegenerativas,

todos los músculos intrínsecos de la laringe están

que conforman las principales poblaciones de

inervados por motoneuronas que tienen sus somas

estudio en la presente Tesis Doctoral.

localizados en el núcleo ambiguo y los axones

- 13 -

utilizado,

el

entorno

(hospitalario,

Introducción____________________________________________________________________ Tabla 1. Causas de disfagia orofaríngea más frecuentes (Modificado de Cook & Kharilas. Gastroenterology 1999) [30]. Envejecimiento Neurológicas: Ictus, esclerosis múltiple, esclerosis lateral amiotrófica, síndrome de Guillain-Barré, enfermedad de Parkinson, demencias, parálisis pseudobulbar, tumores del tronco cerebral, traumatismo craneoencefálico, enfermedad de Huntington, poliomielitis, síndrome postpolio, discinesia tardía, encefalopatías metabólicas. Musculares y reumatológicas: Enfermedad mixta del tejido conectivo (síndrome de superposición), dermatomiositis, miastenia gravis, distrofias musculares, distrofia oculofaringea, poliomiositis, sarcoidosis. Estructurales: Barra cricofaríngea, divertículo de Zenker, membranas cervicales, tumores orofaríngeos, osteofitos y alteraciones esqueléticas, fisura palatina. Metabólicas: Amilodosis, síndrome de Cushing, thyrotoxicosis, enfermedad de Wilson Infecciosas: Difteria, botulismo, enfermedad de Lyme, sífilis, mucositis (herpes, citomegalovirus, candidiasisN) Iatrogénicas: Efectos secundarios de fármacos (quimioterapia, neurolépticos, antidepresivosN), post-quirúrgicas, radioterapia, corrosivas, intubación prolongada.

- 14 -

Introducción Tabla 2. Prevalencia de disfagia orofaríngea (DO). MECV-V, método de exploración clínica volumen viscosidad; UGA, unidad geriátrica de adultos; VFS, videofluoroscopia; FEES, Fibroendoscopia de la deglución. Población diana

Prevalencia de DO

Referencias

Cribado (cuestionarios)

11.4%- 33.7%

Holland 2011 [31] Roy 2007 [32] Bloem 1990 [33] Kawashima 2004 [34] Yang 2013 [35]

Exploración clínica (MECV-V)

23%

Serra-Prat 2011 [36]

Hospitalizados- UGA

No especificado/ test del agua/ MECV-V

29.4% -47%

Lee 1999 [37] Cabré 2014 [38]

Hospitalizados- UGA con neumonía

Test del agua

55%

Cabré 2010 [39]

Institucionalizados, residentes

Cribado (cuestionarios) Test del agua Cribado + exploración clínica

Independientes de la comunidad

Ancianos

Método de evaluación

Fase aguda Ictus

Fase crónica

Enfermedad de Parkinson Neurodegenerativas Demencia

Cribado Exploración clínica Métodos instrumentales Exploración clínica Métodos instrumentales Sintomatología reportada por los pacientes Exploración objetiva Sintomatología reportada por los cuidadores Métodos instrumentales (VFS y FEES)

- 15 -

40%

Nogueira 2013 [40]

38% 51%

Lin 2002 [41]

37 -45% 51 -55% 64% -78%

Martino 2005 [42]

25% -45% 40 -81%

35% Kalf 2012 [43] 82% 19% -30%

Langmore 2007 [44] Ikeda 2002 [45]

57% - 84%

Suh 2009 [46] Langmore 2007 [44] Horner 1994 [47]

Introducción____________________________________________________________________ 5.2 Fisiopatología

deglutorio se combinan con la presencia de factores adicionales, como pueden ser diferentes co-morbididades y/ o sus tratamientos, pueden

5.2.1 La disfagia en el paciente anciano La disfagia en el anciano puede originarse ya sea como consecuencia de cambios en la fisiología deglutoria asociados al envejecimiento, o bien puede ser secundaria a diferentes patologías, mayoritariamente

neurológicas,

altamente

prevalentes en la población anciana. El proceso natural de envejecimiento ocasiona cambios en la anatomía del cuello y de la cabeza, así como en diferentes mecanismos neuronales y musculares, produciéndose una pérdida de la reserva funcional

poner la población anciana en un alto riesgo de padecer disfagia. Por este motivo podemos pensar que de entre los ancianos, el fenotipo frágil [52], que es especialmente vulnerable y susceptible a la enfermedad, presenta uno de los mayores riesgos de padecer DO aunque se desconocen las características fisiopatológicas de la DO en esta población.

5.2.2 La disfagia después de un ictus

que puede afectar el proceso deglutorio. Cuando

Desde

estos cambios en el mecanismo deglutorio se

prevalencia de DO en los ictus hemisféricos

producen en ancianos sanos y robustos, y no

unilaterales es del 40%; en las lesiones bilaterales,

comprometen

de un 56%; en las lesiones de tronco, de un 67%; y

hablamos

la

de

seguridad

de

presbifagia.

No

la

deglución,

obstante,

la

una

perspectiva

neuroanatómica,

la

en lesiones combinadas, de hasta en un 85%

diferenciación entre lo que constituye una deglución

[53;54].

normal y fisiológica en el anciano y hasta qué punto

activación cortical que se presenta en el proceso

estos cambios representan disfagia es difícil de

deglutorio, es la responsable de que después de un

establecer.

ictus hemisférico unilateral, aproximadamente un

Se ha determinado que los ancianos sanos presentan cambios fisiológicos tanto en la fase oral como en la fase faríngea de la deglución. Así pues,

tercio

La

de

asimetría

los

inter-hemisférica

pacientes

desarrollen

en

la

disfagia

orofaríngea, consecuencia de la afectación del hemisferio dominante para la deglución [27].

mientras que las presiones máximas isométricas

La alteración de la seguridad de la deglución en

linguales disminuyen con la edad, las presiones

pacientes con ictus se ha relacionado con un

linguales

la

retraso en el tiempo de cierre del vestíbulo laríngeo

deglución no se ven afectadas [48;49]. Por otro

y de la apertura del UES [8;55]. Un retraso en el

lado, el tiempo necesario para alcanzar el pico de

cierre del vestíbulo laríngeo, aumenta el intervalo

presión también aumenta con la edad, así como se

de tiempo en el que potencialmente puede ocurrir

produce

una aspiración durante la fase faríngea, y un

y

faríngeas

una

generadas

respuesta

motora

durante

orofaríngea los

retraso en la apertura del UES aumenta el volumen

individuos jóvenes. Además de la pérdida de

de bolo acumulado en la hipofaringe, lo que

función motora, se ha descrito que la capacidad de

aumenta el riesgo de rebosar a la vía respiratoria.

discriminación sensorial de la faringe y la laringe

Se

también disminuye con la edad [50;51]. Todos

biomecánicas observadas en los pacientes con DO

estos cambios nos indican una pérdida de reserva

asociada a ictus pueden estar también relacionadas

funcional que si bien en el anciano sano puede ser

con el déficit sensorial que presentan en la

compensada, cuando estos cambios en el proceso

orofaringe y la laringe [56]. Se ha descrito que el

prolongada

y

retrasada

comparada

con

- 16 -

ha

hipotetizado

que

estas

alteraciones

Introducción umbral sensorial de la orofaringe de los pacientes

alteraciones de la eficacia de la deglución, parecen

con disfagia secundaria a un ictus es superior al de

ser más prevalentes [55].

los pacientes con ictus sin disfagia, evidenciando la relevancia

del

trastorno

sensorial

en

la

fisiopatología de la alteración deglutoria [56]. La disfagia

en el

6. DIAGNÓSTICO

ictus también cursa con

alteraciones en la eficacia de la deglución, siendo

El proceso de diagnóstico del paciente con disfagia

común la observación de residuo orofaríngeo en

debe ser abordado de forma integrada por un

esta población, consecuencia de una débil fuerza

equipo

de propulsión del bolo alimentario [55]. Las

identifique, de forma secuencial a los pacientes en

alteraciones deglutorias en los pacientes con ictus

riesgo de disfagia, lleve a cabo evaluaciones

revierten espontáneamente aproximadamente en

clínicas

un 50% de los casos durante las primeras semanas

instrumentales cuando sea necesario.

después del episodio, pero persisten en la otra mitad, lo cual deja a esta población en un alto riesgo

de

complicaciones

respiratorias

[57].

Se

ha

nutricionales descrito

que

y

6.1

multidisciplinar

y

realice

de

profesionales

pruebas

Identificación

del

que

diagnósticas

paciente

vulnerable: cribado

esta

El primer paso del abordaje diagnóstico de la

recuperación de la función deglutoria después de

disfagia es la identificación del paciente vulnerable,

un ictus hemisférico unilateral, está relacionada con

es decir, el paciente con riesgo elevado de padecer

un aumento de la representación motora faríngea

DO. La historia clínica del paciente, una exploración

en el hemisferio contra-lesional [58].

física y los resultados de un test de cribado básico, como son el EAT-10 (Eating Assessment Tool-10)

5.2.3

La

disfagia

en

las

enfermedades

neurodegenerativas Los

pacientes

[59] o el SSQ (Sydney Swallow Questionnaire) [60], son necesarios en este proceso.

con

enfermedades

EAT-10: es un cuestionario de 10 preguntas auto-

neurodegenerativas (Parkinson, esclerosis lateral

administrado

amiotrófica, esclerosis múltiple, etc) representan un

sintomatología, severidad e impacto clínico y social

grupo heterogéneo de pacientes. En general, de

de la disfagia. Cada pregunta puntúa de 0 (ningún

forma

con

problema) a 4 (es un problema serio). De acuerdo

enfermedades neurológicas no progresivas, la

con en el límite superior del intervalo de referencia

alteración de la seguridad de la deglución en

descrito en sujetos sanos, se ha sugerido que una

pacientes con enfermedades neurodegenerativas

puntuación

se ha relacionado con un retraso en el tiempo de

anormalidad [59]. El EAT-10 está traducido y

cierre del vestíbulo laríngeo y de apertura del UES

validado al español [61] (Ver Anexo 1).

similar

que

en

los

pacientes

y la alteración de la eficacia con una débil fuerza de propulsión del bolo alimentario. No obstante, la prevalencia de alteraciones de la seguridad de la deglución en éste grupo de pacientes es inferior que

en

los

pacientes

con

enfermedades

neurológicas no progresivas, mientras que las

por el paciente

final

en

el

que evalúa

EAT-10

≥3

la

indica

SSQ: es un cuestionario de 17 preguntas autoadministrado por el paciente para evaluar la severidad de los síntomas de la disfagia [60]. Cada pregunta se responde en una escala analógica visual horizontal de 100 mm, donde el paciente

- 17 -

Introducción____________________________________________________________________ marca con una X el punto que él cree que

segura y eficaz a los pacientes en riesgo de

representa su grado de disfunción. Se obtiene la

aspiraciones. Los signos de alteración de la

puntuación

pregunta,

seguridad de la deglución evaluados son: tos,

midiendo la distancia en mm desde el origen de la

cambios de voz y desaturación de oxígeno ≥3%.

escala hasta la X marcada por el paciente.

Los signos de alteración de la eficacia de la

correspondiente

a

cada

Se desconoce la precisión diagnóstica de ambos cuestionarios para la detección clínica de la disfagia y tampoco se han realizado estudios específicos para determinar los puntos de corte de cada cuestionario que indica DO. Todo aquel paciente que sea identificado en riesgo de disfagia en esta etapa del proceso, debe ser referido a una

deglución evaluados son: la eficacia del sello labial, presencia de residuo oral, deglución fraccionada y síntomas de residuo faríngeo. El MECV-V es una prueba de esfuerzo en la cual se administran una serie

de

bolos

de

diferentes

volúmenes

y

viscosidades, en orden creciente de dificultad. El test

se

empieza

administrando

un

bolo

de

viscosidad néctar a un volumen de 5 mL,

exploración deglutoria más exhaustiva.

continuando con la administración de volúmenes de

6.2

10 mL y 20 mL; se continúa con una serie de bolos

Exploración clínica

El objetivo principal de los métodos de exploración clínica para la DO es recoger los datos necesarios para establecer un diagnóstico clínico. Además, debe permitirnos

evaluar la fisiopatología de la

enfermedad, para identificar los principales signos y

de líquido a los mismos volúmenes y finalmente con la serie de pudin. Si el paciente presenta signos de alteración de la seguridad de la deglución en algún bolo, la serie se interrumpe y se continúa con pudín o finaliza la exploración (Figura 8).

síntomas de DO y el mecanismo de disfunción de la

La precisión diagnóstica del MECV-V se ha

deglución, seleccionar aquellos pacientes que

validado

deben ser referidos a una exploración instrumental

videofluoroscopia, usando espesantes de almidón

y/o seleccionar el tratamiento más adecuado para

modificado. En la Tabla 3 se muestran los valores

los pacientes que no pueden someterse fácilmente

de sensibilidad, especificidad y valores predictivos

a

positivo y negativo de los principales signos de

una

videofluoroscopia

(VFS)

o

a

una

Uno de los métodos de exploración clínica que estos

Exploración

criterios Clínica

es

el

Volumen

Método

al

test

de

referencia

alteración de la seguridad y de la eficacia de la

fibroendoscopia de la deglución (FEES).

cumple

frente

de

-Viscosidad

deglución. La precisión diagnóstica del test con espesantes de goma xantana se desconoce. El

test del

agua es

también una de

las

(MECV-V o V-VST de las siglas del inglés Volume-

herramientas históricamente más utilizadas para

Viscosity Swallow Test).

realizar la exploración clínica de la deglución

El MECV-V fue diseñado por Clavé y Arreola [62] para identificar los principales signos y síntomas clínicos de alteración de la eficacia y de la seguridad de la deglución, permitiendo establecer la viscosidad ideal para ser administrada de forma

[63;64]. En su forma más común, consiste en que el paciente debe beber 90 mL de agua de un vaso sin interrupción. Es un test que presenta una alta sensibilidad para detectar aspiraciones (94%-96%) pero una baja especificidad (26%-46%).

- 18 -

Introducción

Figura 8. Algoritmo del MECV-V. Izquierda: los pacientes con deglución segura completan toda la exploración. Medio: diagrama representativo de pacientes con alteración de la seguridad de la deglución a 10 mL nectar. Derecha: diagrama representativo de pacientes con alteración de la seguridad a 10 mL líquido. Reproducido de Rofes et al (2012) [65].

Tabla 3. Sensibilidad, especificidad y valores predictivos del MECV-V en pacientes con disfagia. Reproducido de Clavé et al (2008) [62]. Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

Impaired safety

88.2

64.7

90.9

57.9

Impaired efficacy

100

28.8

28.8

100

Penetration

83.7

64.7

87.2

57.9

Oral Residue

69.2

80.6

39.1

93.5

Pharyngeal Residue

86.4

34.6

75.0

52.9

- 19 -

Introducción________________________________________ ____________________________ 6.3

Técnicas instrumentales

Cuando no hay entrada de material a la vía respiratoria, se asigna una puntuación de 1; las penetraciones se clasifican de 2 a 5: cuando se

6.3.1 Videofluoroscopia La VFS es una técnica radiológica dinámica que consiste en la obtención de una secuencia de imágenes en perfil lateral (y antero-posterior si es necesario) de la cavidad oral, la faringe, la laringe y el esófago cervical de un paciente mientras traga una serie de bolos, de contraste hidrosoluble o sulfato de bario, que pueden presentarse a diferentes volúmenes y viscosidades. Actualmente se considera la técnica de referencia para el estudio de la DO. El análisis imagen por imagen de la secuencia videofluoroscopica permite realizar estudios tan cualitativos (signos de alteración de la fase oral y de la fase faríngea de la deglución) como cuantitativos (cronología de la respuesta motora

orofaríngea,

cinemática

del

bolo,

movimiento de las estructuras deglutorias como son el hioides y la laringe) de la deglución. Durante la exploración videofluoroscópica se puede también evaluar

el

terapéuticas.

efecto Los

de

diferentes

principales

signos

estrategias VFS

de

alteración de la eficacia evaluados son el residuo orofaríngeo, definido como presencia de contraste radiológico en la boca o la faringe (incluyendo vallécula y senos piriformes) una vez terminada la deglución. Los principales signos VFS de alteración de la seguridad de la deglución son la presencia de penetraciones en el vestíbulo laríngeo (el contraste

produce entrada de material al vestíbulo laríngeo pero sin que llegue a contactar cuerdas vocales y no deja residuo en la vía aérea, se asigna una puntuación de 2; cuando se produce entrada de material a la vía respiratoria, no contacta cuerdas vocales

pero

deja

residuo,

se

asigna

una

puntuación de 3; cuando se produce entrada de material al vestíbulo laríngeo, contacta cuerdas vocales pero sin rebosarlas y no deja residuo, se asigna una puntuación de 4; cuando se produce entrada de material al vestíbulo laríngeo, contacta cuerdas vocales pero sin rebasarlas y deja residuo, se asigna una puntuación de 5; las aspiraciones se clasifican del 6 al 8: cuando el material rebasa las cuerdas vocales, se produce tos y esta tos es efectiva expulsando el material de la vía aérea, se asigna una puntuación de 6; cuando el material traspasa las cuerdas vocales, se produce tos y esta tos no es efectiva expulsando el material de la vía aérea, se asigna una puntuación de 7; cuando el material traspasa las cuerdas vocales y no se produce tos (aspiración silente), se asigna una puntuación de 8. Cabe destacar que se considera deglución segura cuando obtenemos puntuaciones de 1 o 2, ya que las penetraciones de grado 2 no se consideran

patológicas

y

son

comúnmente

observadas en voluntarios sanos.

radiológico entra dentro del vestíbulo laríngeo pero

El movimiento del hioides tanto vertical como

no traspasa las cuerdas vocales) y las aspiraciones

anterior se puede monitorizar trazando un eje de

traqueobronquiales (el contraste radiológico entra

coordenadas, tomando como origen del eje la

en el vestíbulo laríngeo y traspasa las cuerdas

esquina anterior -inferior de la vértebra C3 y siendo

vocales). Las alteraciones de la seguridad de la

el eje de ordenadas la línea que conecta las

deglución se clasifican de acuerdo con la escala de

esquinas anterior -inferior de las vértebras C3 y C5

Penetración-Aspiración

[8].

(PAS)

descrita

por

Rosenbeck et al en 1997 [66] y que tiene en cuenta tanto el nivel de penetración de contraste a la vía respiratoria

como

la

respuesta

del

paciente.

La velocidad media del bolo alimentario a través de la faringe puede calcularse como el tiempo que pasa des de que la cabeza del bolo traviesa el sello

- 20 -

Introducción glosopalatino hasta que llega al UES dividido entre

técnica, como que no es posible evaluar la fase oral

la distancia que los separa; la velocidad final del

de la deglución así como el hecho que durante la

bolo a nivel del UES se calcula de acuerdo con la

deglución, existe visibilidad restringida debido a que

ecuación: v = v0 + at, donde v0 es el valor inicial de

el endoscopio entra en contacto con la base de la

velocidad que se considera 0, a es la aceleración

lengua, la epiglotis y el propio bolo lo que puede

adquirida por el bolo alimentario a nivel del UES (y

impedir la visualización directa de penetraciones y

calculada según la expresión del movimiento

aspiraciones durante la deglución [67].

rectilíneo uniformemente acelerado desglosada abajo) y t es el tiempo que tarda la cabeza del bolo

6.3.3 Manometria faringoesofágica de alta

alimentario en llegar al UES. La fuerza de

resolución

propulsión del bolo alimentario puede determinarse mediante la segunda ley de Newton,

F = ma,

donde F es la fuerza a la que el bolo es propulsado por la lengua, m es la masa del bolo administrado en cada caso y a es la aceleración adquirida por el bolo alimentario a nivel del UES y obtenida a partir de

la

expresión

del

movimiento

rectilíneo

uniformemente acelerado s = s0 + v0 (t- t0 ) + ½ a 2

(t- t0) donde s es la distancia entre el sello glosopalatino y el UES, t es el tiempo que ha tardado el bolo alimenticio en recorrer s; s0 , t0 y v0 son los valores iniciales de espacio, tiempo y velocidad respectivamente, que se asume que

La manometría faringoesofágica de alta resolución permite el estudio cuantitativo de las presiones a nivel de la faringe y UES. Los parámetros que se pueden medir con esta técnica son la amplitud de la contracción faríngea, la amplitud de la relajación del UES y la coordinación entre ambos. Resulta de especial utilidad cuando se asocia a la VFS sobre todo para el estudio de las alteraciones de apertura del UES. La técnica utiliza un catéter que incorpora una serie de

sensores

de

presión

de

estado

sólido

posicionados en la faringe, UES y cuerpo esofágico colocados cada 1 ó 2 centímetros, de forma que,

tienen valor 0.

por interpolación entre ellos, la presión intraluminal puede llegar a ser mostrada de forma continua en

6.3.2 Fibroendoscopia de la deglución (FEES) La

FEES

(del

inglés

Fiberoptic

endoscopic

evaluation of swallowing) ofrece al profesional de la

el espacio. Las medidas de presión se muestran en unos mapas topográficos de presión [68].

disfagia una herramienta fiable para investigar la deglución.

Se

utiliza

un

fibroscopio

flexible

7. TRATAMIENTO

conectado a una fuente de luz y un aparato de vídeo para grabar la secuencia de imágenes deglutorias. Es bien tolerado, fácilmente repetible y se puede realizar en la cabecera del paciente. Existen varios protocolos para la FEES en los que, igual que en la VFS, pueden utilizarse diferentes consistencias y volúmenes de bolo, que se administrarán teñidos con colorante alimentario, así como evaluar diferentes estrategias terapéuticas. Sin embargo, existen algunas limitaciones de la

El tratamiento del paciente con disfagia orofaríngea tiene

dos

objetivos

complicaciones

que

principales:

prevenir

las

podrían

derivarse

a

consecuencia de la disfunción deglutoria presente, cómo son la malnutrición, la deshidratación y la neumonía aspirativa, y en segundo lugar y siempre que sea posible, revertir la disfunción deglutoria de forma que pueda administrarse una dieta lo menos restrictiva posible. Focalizadas en el primer objetivo

- 21 -

Introducción________________________________________ ____________________________ higiénico-dietéticas

reevaluarse y reajustarse regularmente. La British

básicas y las estrategias compensatorias. Con el

Dietetic Association y el Royal College of Speech

objetivo añadido de revertir la disfunción deglutoria

and

encontramos las estrategias rehabilitadoras, los

modificaciones de la textura de los sólidos en

tratamientos quirúrgicos y las estrategias de neuro-

cuatro categorías: textura B, C, D y E [70]. La

estimulación.

textura B se refiere a una dieta puré fino, que no

encontramos

las

medidas

Language

Therapists

clasifican

las

puede comerse con tenedor porque no mantiene la

7.1 Medidas higiénico-dietéticas

consistencia; textura C corresponde a textura de

Las recomendaciones generales para el paciente

puré espeso o denso que sí que mantiene la

con dificultades en la deglución consisten en

consistencia y que por lo tanto, puede ser comido

repartir la alimentación en 5 ó 6 comidas diarias,

con tenedor; textura D descrita como una dieta

que deben realizarse con el paciente en estado de

picada fina, no triturada, contiene alimentos suaves,

alerta. Se debe asegurar una postura correcta del

tiernos y húmedos que requieren cierta masticación

paciente, sentado con la espalda recta y la cabeza

y que puede acompañarse con una salsa cremosa

ligeramente

el

densa; textura E blanda, con alimentos enteros que

momento de tragar; la comida debe producirse bajo

requieren masticación pero que puede aplastarse

supervisión pero fomentando la autoalimentación,

con un tenedor e ir acompañados con una salsa

en un ambiente tranquilo y relajado. Se deben

cremosa menos espesa. Por otro lado, la American

evitar alimentos con dobles texturas y de riesgo

Dietetic Association publicó en 2002 la National

(alimentos que mezclen líquidos y sólidos, que

Dysphagia Diet en la que se consideran cuatro

puedan fundirse, pegajosos, que se desmenucen o

posibles tipos de dieta: el nivel 1 corresponde a

fragmenten con facilidadN). Se debe considerar la

dieta puré; el nivel 2, consiste es una dieta de fácil

recomendación de suplementos nutricionales en el

masticación con alimentos blandos, troceados,

caso de riesgo de malnutrición. Es también

húmedos y de fácil formación del bolo; el nivel 3 es

importante establecer unas recomendaciones de

una dieta que permite la administración de

higiene oral mínimas que incluyan cepillado dental

alimentos en condiciones normales exceptuando

diario y el uso de colutorios antisépticos en

aquellos

pacientes con DO ya que la colonización de la

crujientes; y el nivel 4 se considera una dieta

cavidad oral por patógenos respiratorios, junto con

normal [71].

la presencia de aspiraciones y la fragilidad, son

En aquellos casos en los que la vía oral no sea

factores de riesgo de neumonía por aspiración (AP)

segura y no permita cubrir los requerimientos

en pacientes ancianos con DO [69].

nutricionales necesarios, pero se mantenga la

inclinada

hacia

adelante

en

alimentos

más

duros,

pegajosos

o

capacidad funcional intestinal, se considerará la

7.2 Estrategias compensatorias

alimentación enteral mediante la colocación de sondas nasoentéricas o de enterostomías. El

7.2.1 Adaptación de la dieta

sondaje

intragástrico

transnasal

con

sondas

nasogástricas es de elección para administrar los

7.2.1.1 Adaptación de los sólidos

nutrientes directamente en el estómago durante

Las adaptaciones de la dieta deben personalizarse

períodos de tiempo inferiores a 6 semanas; en

a la capacidad deglutoria del paciente y deben

cambio, para aquellos pacientes con perspectivas

- 22 -

Introducción de soporte nutricional mantenido durante un largo

terapéutico, el aumento de la viscosidad del bolo

período de tiempo, la mejor opción es la colocación

con espesantes de almidón aumenta el residuo

de una gastrostomía endoscópica percutánea

orofaríngeo

(PEG). Ambas estrategias de nutrición permiten la

pacientes con propulsión del bolo deficiente como

administración de fórmulas de nutrición enteral

los pacientes ancianos

adaptadas a los requerimientos del paciente [72].

enfermedades neurodegenerativas. Esto podría

post-deglutorio,

aumentar

7.2.1.2 Adaptación de los líquidos

el

deglutorias.

riesgo

Otra

especialmente

en

y los pacientes con de

aspiraciones

desventaja

de

los

postlíquidos

Una de las intervenciones compensatorias básicas

espesados a base de almidón es que, en general,

en

no son bien aceptados por los pacientes y el grado

hospitales

e

instituciones

sanitarias

para

aumentar la seguridad de la deglución y evitar

de cumplimiento de su prescripción es bajo [76].

aspiraciones es espesar los líquidos. Se ha descrito

A pesar del uso generalizado de los espesantes en

que el aumento de la viscosidad de los líquidos con

la práctica clínica, existe una falta de consenso en

espesantes de almidón modificado reduce las

los descriptores de las viscosidades a nivel

penetraciones en el vestíbulo laríngeo y las

internacional. La Tabla 4 muestra los estándares

aspiraciones traqueobronquiales [55;73], con la

de viscosidad descritos por diferentes sociedades.

consiguiente

reducción

en

la

incidencia

de

neumonía por aspiración [74]. Se ha propuesto que ralentizar la velocidad del bolo a través de la faringe es el principal mecanismo de acción de los espesantes para proteger contra las aspiraciones [75]. Sin embargo, en paralelo a su efecto

Numerosos

estudios

manifiestan

además

dificultad de preparar mezclas ajustadas a los descriptores establecidos, así como reproducir las texturas usadas en el estudio VFS, lo cual hace que los pacientes reciban frecuentemente una textura inadecuada.

Tabla 4: Comparación de terminologías internacionales para líquidos espesados. LÍQUIDO AUSTRALIA

IRLANDA

UK EEUU

NÉCTAR

MIEL

PUDIN

Mildly thick

Moderately thick

Extremely thick

(150 mPa s)

(400 mPa s)

(900 mPa s)

Grade 2-

Grade 3-

Grade 4-

Mildly thick

Moderately thick

Extremely thick

(150 mPa s)

(400 mPa s)

(900 mPa s)

Thickened fluid

Thickened fluid

Thickened fluid

Stage 1

Stage 2

Stage 3

Thin

Nectar-like

Honey-like

Spoon-thick

(1 -50 mPa s)

(51–350 mPa s)

(351–1750 mPa s)

>1750 mPa s

Regular

Regular

Thin

la

- 23 -

Introducción________________________________________ ____________________________ paladar y musculatura suprahioidea). Una de las

7.2.2 Estrategias posturales La adopción de cambios posturales durante la deglución es una estrategia ampliamente usada en el paciente con DO. Permiten modificar la dirección del bolo alimentario, traduciéndose en un mejor transporte y en una reducción de las aspiraciones y del residuo orofaríngeo. Sin embargo, y a pesar de su amplio uso en la práctica clínica, la literatura

praxias más conocidas es la maniobra de Shaker que permite potenciar la musculatura hioidea y consigue un efecto terapéutico por incrementar la apertura anteroposterior del UES, disminuyendo el residuo y las aspiraciones post-deglutorias [85].

7.3.2 Estimulación eléctrica neuro-muscular

disponible muestra controversias en los beneficios

La

de

estrategias

neuromuscular (NMES) ha sido propuesta como

posturales más utilizadas son la flexión anterior del

tratamiento para la disfagia orofaríngea [86], siendo

cuello [78;79], flexión posterior del cuello [80] y

ampliamente usada en EEUU, pero no muy

rotación e inclinación de la cabeza hacia el lado

conocida todavía en Europa. La terapia implica la

paralizado [81].

aplicación de estimulación eléctrica a través de dos

estas

estrategias

[77].

Las

terapia

mediante

estimulación

eléctrica

electrodos de superficie colocados en el cuello, pudiéndose colocar en diferentes configuraciones.

7.2.3 Maniobras deglutorias Las

maniobras

son

estrategias

específicas

encaminadas a compensar alteraciones fisiológicas durante la deglución con el objetivo de proteger la vía aérea, facilitar el cierre laríngeo y facilitar el paso del bolo hacia el esófago sin dejar residuo. Son

maniobras

voluntarias

que

requieren

el

aprendizaje y la colaboración activa del paciente. Los estudios disponibles hasta la actualidad son limitados,

contradictorios

y

con

muestras

poblacionales pequeñas [82;83]. Las maniobras más utilizadas son: la deglución supraglótica, la deglución supersupraglótica, la deglución forzada, la maniobra de Mendelsohn y la maniobra de Masako [84].

En general, se aplican pulsos eléctricos bifásicos de 300 µs con una frecuencia de 80 Hz y una amplitud de entre 2,5 y 25 mA dependiendo de la tolerancia del paciente. Las sesiones de tratamiento TM

suelen durar unos 60 minutos. VitalStim

es uno

de los dos aparatos para NMES aprobados por la FDA (Junio 2001) para el tratamiento de la disfagia. Los datos presentados en la publicación inicial [86] mostraron en una población de 110 pacientes que presentaban problemas de deglución después de haber sufrido un ictus, el tratamiento con NMES era seguro y efectivo. Desde ese momento, varios han sido los estudios publicados evaluando la terapia de NMES presentando resultados discordantes. En un meta-análisis realizado en

2007 [87] se

evaluaron los 7 estudios clínicos realizados hasta el

7.3 Estrategias rehabilitadoras

momento con un total de 255 pacientes con disfagia asociada a múltiples etiologías, tratados

7.3.1 Praxias neuromusculares Las

praxias

neuromusculares

consisten

en

repeticiones de ejercicios orofaciales y de cuello que buscan mejorar la fisiología de la deglución, dirigidos a mejorar la movilidad, el tono muscular, la sensibilidad

y

la motricidad de

los órganos

implicados en la deglución (labios, lengua, velo del

con NMES [86;88-92] encontrando una pequeña significación

estadística

en

la

mejora

de

la

deglución de los pacientes tratados con NMES. Los resultados

del

meta-análisis

deben

ser,

sin

embargo, tratados con cuidado ya que no se incluyen estudios controlados randomizados, sólo

- 24 -

Introducción pequeños estudios controlados no randomizados y estudios

de

serie

de

casos

abiertos.

La

heterogeneidad de los estudios con respecto a la duración del tratamiento, el número de sesiones realizadas, el emplazamiento de los electrodos y el método de evaluación del resultado terapéutico también debe ser considerado, sugiriendo la necesidad de realizar una investigación más rigurosa en este campo.

7.5 Estrategias de neuro-estimulación En los últimos años, han surgido un conjunto de nuevas

estrategias

destinadas

a

mejorar

la

deglución de los pacientes con DO basadas en la neuro-estimulación y la neuro-rehabilitación. Su objetivo es estimular la plasticidad cortical y restaurar la fisiología deglutoria deteriorada. Se pueden clasificar en las que estimulan directamente la corteza motora faríngea y las vías corticobulbares (las técnicas de estimulación cerebral no

7.4 Tratamientos quirúrgicos

invasivas) y las que promueven la neuro-plasticidad

En algunas situaciones específicas, el tratamiento

mediante

quirúrgico está indicado para revertir la disfunción

orofaríngeo

deglutoria. La realización de una miotomía del UES,

farmacológicos o químicos.

el

aumento por

del

medios

estímulo físicos,

sensorial eléctricos,

se ha considerado el tratamiento de elección en pacientes con DO que presentan una alteración en

7.5.1 Estrategias de estimulación sensorial

la apertura del esfínter con disminución de la

periféricas

distensibilidad e incremento de la resistencia al flujo y adecuada propulsión lingual y faríngea. También en pacientes con divertículo de Zenker se ha asociado

a

la

normalización

de

la

presión

hipofaríngea y la distensibilidad del UES. Los resultados de la intervención son buenos en pacientes sin antecedentes neurológicos y con respuesta motora orofaríngea preservada.

7.5.1.1 Estímulos químicos Acidificación

del

bolo

alimentario:

La

acidificación del bolo alimentario fue una de las primeras estrategias que se utilizó para estimular la respuesta deglutoria en pacientes con DO asociada a ictus y otras enfermedades neurológicas. Se ha asociado a una reducción en el tiempo de tránsito

La inyección transcutánea de toxina botulínica

oral, el tiempo de retraso faríngeo, mejora de la

(Toxina

eficacia de la deglución [95] y reducción de la

Botulínica

Tipo

A)

en

el

UES

ha

demostrado ser un procedimiento seguro y con

prevalencia

buenos

[95;96].

resultados

(mejoría

de

la

disfagia,

disminución de episodios de aspiración) en los pacientes con disfunción del cricofaríngeo asociada a disfagia neurógena [93].

de

aspiraciones

y

penetraciones

Picante: la adición de ingredientes picantes, tales como la capsaicina (Capsicum sp) o la piperina (Piper nigrum) al bolo alimentario también han sido

En casos de parálisis de una cuerda vocal, puede

probados en pacientes con disfagia para evaluar su

ser tratado por medialización del pliegue con

efecto terapéutico. La administración aguda de

métodos de inyección transendoscópica, transoral o

capsaicina (10

percutánea o por medio de una laringoplastia de

deglutoria

modo que la cuerda contralateral pueda completar

instilación de 1 mL de agua destilada en la faringe

el cierre laríngeo [94].

hasta el inicio de la deglución) [97]. Por otra parte,

-8

-6

-10

(tiempo

que

M) reduce la latencia transcurre

desde

la

la administración diaria de capsaicina durante un

- 25 -

Introducción________________________________________ ____________________________ -6

mes (10

M) también acortó la latencia deglutoria

La estimulación eléctrica transcutánea mediante

en pacientes ancianos con disfagia, sobre todo en

estímulos eléctricos de baja intensidad y evitando la

las personas mayores con alto riesgo de aspiración

contracción

[98]. Por otro lado, 30 días de estimulación olfativa

también se ha utilizado como una estrategia

con aceite de pimienta negra también acortan la

sensorial [104]. Esta estrategia de estimulación

latencia deglutoria en un grupo de pacientes con

sensorial ha mostrado una mejora significativa en

disfagia después de un ictus [99].

varios parámetros deglutorios, como el tiempo de

Otros estímulos químicos usados en pacientes con DO son los líquidos carbonatados [100] y el mentol

[101],

así

como

combinaciones

de

diferentes estímulos. Todos estos compuestos ejercen su acción mayoritariamente a través de una familia de receptores-canales trans-membrana, los

respuesta

muscular

deglutoria

durante

y

la

el

tratamiento,

prevalencia

de

aspiraciones en pacientes con disfagia post-ictus [104], pero no en pacientes con disfagia con la enfermedad de Parkinson [105].

7.5.2 Estrategias de estimulación central

Transient Receptor Potencial Channels (TRP)

El objetivo de las técnicas de estimulación central

[24], que se expresan en las neuronas sensoriales

es

primarias de la orofaringe [19], aumentando el

estimulación directa de la corteza cerebral. Las

estímulo sensorial a los núcleos centrales de la

técnicas de estimulación cerebral no invasivas

deglución del tronco cerebral y a la corteza

incluyen la estimulación magnética transcraneal

cerebral, lo que, potencialmente, podría promover

repetitiva (rTMS) y la estimulación transcraneal

la reorganización neuronal y facilitar la activación

directa

de la respuesta deglutoria.

prometedores en los primeros estudios realizados

inducir

la

(tDCS),

neuroplasticidad

ambas

cortical

mostrando

por

resultados

[106-108]. En el Anexo 2 se presenta un artículo

7.5.1.2 Estímulos eléctricos

Editorial en el que se discuten

Estudios en animales y en humanos han reflejado que la aplicación de estímulos eléctricos en las

las posibles

implicaciones futuras de estos tratamientos en el campo de la disfagia [109].

áreas inervadas por el nervio glosofaríngeo (IX) y el vago (X) facilita la respuesta deglutoria [18;102]. En

8. COMPLICACIONES

pacientes con DO post-ictus, la aplicación de tres sesiones

de

un

estímulo

eléctrico

a

nivel

intrafarígeo (5Hz durante 10 minutos) ocasiona una reducción del tiempo de tránsito faríngeo y del riesgo de aspiraciones relacionándose con un incremento en la excitabilidad faríngea a nivel cortico-bulbar y de la representación cortical en el hemisferio

no

dañado

por

el

accidente

cerebrovascular. La terapia se ha relacionado con un mejor pronóstico clínico, con una mejora del estado nutricional y reducción de la estancia hospitalaria durante el episodio agudo [103].

La disfagia orofaríngea es un factor de mal pronóstico para los pacientes que la padecen: los pacientes

ingresados

con

disfagia

presentan

hospitalizaciones más largas, mayor número de complicaciones, mayor utilización de recursos y mayor porcentaje de institucionalización después del ingreso [110]. A pesar de que la disfagia es sólo un síntoma, la disfución orofaríngea subyacente que la origina puede conducir a dos grupos de complicaciones de gran relevancia clínica, con una alta mortalidad asociada. El deterioro de la eficacia

- 26 -

Introducción de la deglución puede conducir a la malnutrición del

realizar la evaluación y el cribado nutricional en las

paciente debido a que no ingiera los requerimientos

diferentes poblaciones. El test Mini Nutricional

nutricionales adecuados, y la alteración de la

Assessment (MNA®) [116] es una herramienta

seguridad de la deglución puede cursar con el

válida para evaluar el estado nutricional de los

desarrollo de infecciones respiratorias recurrentes y

ancianos. Está integrado por 18 ítems que abarcan

neumonía por aspiración.

la evaluación antropométrica (peso, talla, y pérdida de peso), evaluación general (estilo de vida,

8.1 Malnutrición

medicamentos y movilidad), evaluación de la dieta

El deterioro de la eficacia de la deglución puede

(número de comidas, alimentos e ingesta de

reducir

la

líquidos), autonomía a la hora de comer y auto-

malnutrición. En una reciente revisión se ha

percepción de la salud y el estado nutricional. La

reportado que los pacientes con ictus y disfagia

versión corta del MNA® (MNA® Short-Form,

presentan 2.4 veces más de riesgo de desarrollar

MNA®-SF) [117] (ver Anexo 1) está formada por

malnutrición que los que no tienen disfagia [111].

las primeras 6 preguntas del test, conserva la

La relación entre DO y malnutrición es también

precisión y validez de la versión larga y puede ser

evidente en la población anciana, tanto en la que

completada en menos de 5 minutos. Actualmente,

vive en la comunidad [36], en la hospitalizada [112],

el MNA®-SF es la versión preferida del MNA® en la

como en la institucionalizada [113]. También en

práctica clínica habitual en el ámbito comunitario,

enfermedades neurodegenerativas como la de

hospitalario y en centros de larga estancia, debido

Parkinson, la presencia de DO podría ser un factor

a su facilidad de uso y practicidad.

asociado al peor estado nutricional de estos

Otras

pacientes [114].

recomendadas por la ESPEN (The European

La malnutrición contribuye al peor pronóstico de la

Society for Clinical Nutrition and Metabolism) son el

enfermedad ya que empeora el sistema inmune, la

MUST para los adultos de la comunidad y el NRS-

función muscular y retrasa la posible recuperación.

2002 para los pacientes hospitalizados [118].

la

alimentación

oral

y

llevar

a

Una Resolución del Consejo de Europa sobre la alimentación y la nutrición en los hospitales afirma

herramientas

de

cribado

nutricional

8.2 Neumonía por aspiración

que la malnutrición en los pacientes hospitalizados

El término "neumonía por aspiración," se refiere

también conduce a hospitalizaciones prolongadas,

específicamente al desarrollo de un infiltrado

disminución en la calidad de vida y costos

radiográficamente evidente en los pacientes que

innecesarios de atención sanitaria, e identifica la

están en riesgo de aspiración orofaríngea [119]. La

disfagia

importante

aspiración de pequeñas cantidades de secreciones

contribuyente a la malnutrición [115]. Es, por tanto,

orofaríngeas durante el sueño es un hallazgo

necesario evaluar el estado nutricional de los

común en adultos sanos

pacientes con DO e identificar aquellos pacientes

acaba conduciendo a complicaciones debido a la

malnutridos o que estén en riesgo de malnutrición

baja

para poder realizar las intervenciones pertinentes.

secreciones faríngeas normales, junto con un

La

la

transporte ciliar activo, y a un sistema inmune

intervención temprana mejoran el pronóstico de los

humoral y celular normal (gracias en parte a un

pacientes. Existen diferentes herramientas para

buen estado nutricional). Sin embargo, cuando se

orofaríngea

evaluación

del

como

estado

un

nutricional

y

- 27 -

carga

de

bacterias

que generalmente no patógenas

en

las

Introducción________________________________________ ____________________________ aspiran

volúmenes

deglución,

en

un

importantes paciente

durante

con

un

la

Referencias

estado

inmunológico alterado, y alta carga microbiana

1.

Standring S, Borley NR, Collins P, Crossman AR, Gatzoulis MA, Healy JC, et al. Oral Cavity. Gray's Anatomy: The Anatomical Basis of Clinical Practice. 40th ed. Amsterdam: Elsevier Limited; 2008.

2.

Drake RL, Vogl WA, Mitchell AWM. Head and Neck. Gray's Anatomy for Students. 2nd ed. Amsterdam: Elsevier Inc; 2005.

3.

Standring S, Borley NR, Collins P, Crossman AR, Gatzoulis MA, Healy JC, et al. Pharynx. Gray's Anatomy: The Anatomical Basis of Clinical Practice. 40th ed. Amsterdam: Elsevier Limited; 2008.

4.

Standring S, Borley NR, Collins P, Crossman AR, Gatzoulis MA, Healy JC, et al. Larynx. Gray's Anatomy: The Anatomical Basis of Clinical Practice. 40th ed. Amsterdam: Elsevier Limited; 2008.

5.

Cook IJ, Dodds WJ, Dantas RO, Massey B, Kern MK, Lang IM, et al. Opening Mechanisms of the Human Upper Esophageal Sphincter. Am J Physiol 1989;257:G748-G759.

6.

Singh S, Hamdy S. The upper oesophageal sphincter. Neurogastroenterol Motil 2005;17:3-12.

7.

Massey BT. Physiology of oral cavity, pharynx and upper esophageal sphincter. GI Motility online 2006 [cited 2013 Sep 1]; Available from: http://goo.gl/5X4Nkx

8.

Kahrilas PJ, Lin S, Rademaker AW, Logemann JA. Impaired deglutitive airway protection: a videofluoroscopic analysis of severity and mechanism. Gastroenterology 1997;113:1457-64.

9.

Rofes L, Arreola V, Almirall J, Cabre M, Campins L, Garcia-Peris P, et al. Diagnosis and management of oropharyngeal dysphagia and its nutritional and respiratory complications in the elderly. Gastroenterol Res Pract 2011;2011. http://dx.doi.org/10.1155/2011/818979

10.

Logemann JA, Kahrilas PJ, Cheng J, Pauloski BR, Gibbons PJ, Rademaker AW, et al. Closure mechanisms of laryngeal vestibule

patógena en la orofaringe, consecuencia de una mala higiene oral, puede desarrollarse la neumonía. La neumonía es una de las principales causa de muerte en pacientes que han sufrido un ictus [120;121], siendo la disfagia, y más aún la presencia de aspiraciones, factores de riesgo conocidos para el desarrollo de neumonía en pacientes con ictus [42]. También en pacientes con enfermedades

neurodegenerativas

como

la

enfermedad de Parkinson, la neumonía es una de las principales causas de muerte [122] aunque su relación con la disfagia no ha sido específicamente estudiada. En ancianos, la neumonía es también una de las principales causas de morbilidad y mortalidad en los países desarrollados. Se ha descrito que la neumonía por aspiración es un importante

mecanismo

patogénico

para

la

neumonía en ancianos, tanto la adquirida en la comunidad

(CAP)

como

la

adquirida

en

instituciones sanitarias y que el ratio de neumonías por aspiración versus cualquier otro tipo de neumonía aumenta con la edad [123]. Se ha descrito en estudios previos diferentes factores de riesgo de NAC en el anciano, relacionados con el estilo de vida del paciente como el tabaquismo y el consumo de alcohol, la mala situación funcional y nutricional, la pérdida de peso y el uso de inmunosupresores, con co-morbididades como la insuficiencia cardíaca, la enfermedad renal y la enfermedad pulmonar obstructiva crónica (COPD) y con las exposiciones ambientales al humo del tabaco, gases, vapores y sustancias químicas [124126]. Sin embargo, el papel de la disfagia orofaríngea como factor de riesgo en el desarrollo de neumonía adquirida en la comunidad en el anciano no ha sido específicamente investigado.

- 28 -

Introducción during swallow. Am J Physiol 1992;262:G338G344.

Pepper Components. Biosci Biochem 2010;74:1068-72.

Biotechnol

11.

Logemann JA. Mechanisms of Normal and Abnormal Swallowing. Cummings Otolaryngology Head and Neck Surgery. 5th ed. Amsterdam: Elsevier Inc; 2010.

22.

Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, et al. A TRP channel that senses cold stimuli and menthol. Cell 2002;108:705-15.

12.

Kahrilas PJ, Lin SZ, Logemann JA, Ergun GA, Facchini F. Deglutitive Tongue Action Volume Accommodation and Bolus Propulsion. Gastroenterology 1993;104:15262.

23.

Mckemy DD, Neuhausser WM, Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 2002;416:52-8.

24. 13.

Kahrilas PJ, Logemann JA, Lin S, Ergun GA. Pharyngeal clearance during swallowing: a combined manometric and videofluoroscopic study. Gastroenterology 1992;103:128-36.

Vay L, Gu CJ, McNaughton PA. The thermoTRP ion channel family: properties and therapeutic implications. Br J Pharmacol 2012;165:787-801.

25. 14.

Ertekin C, Kiylioglu N, Tarlaci S, Keskin A, Aydogdu I. Effect of mucosal anaesthesia on oropharyngeal swallowing. Neurogastroenterol Motil 2000;12:567-72.

Netter FH. Head and Neck. Atlas of Human Anatomy. 6th ed. Amsterdam: Elsevier Inc; 2014.

26.

Steele CM, Miller AJ. Sensory Input Pathways and Mechanisms in Swallowing: A Review. Dysphagia 2010;25:323-33.

Jean A. Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev 2001;8:929-69.

27.

Hamdy S, Aziz Q, Rothwell JC, Singh KD, Barlow J, Hughes DG, et al. The cortical topography of human swallowing musculature in health and disease. Nat Med 1996;2:121724.

28.

Hamdy S, Rothwell JC, Brooks DJ, Bailey D, Aziz Q, Thompson DG. Identification of the cerebral loci processing human swallowing with H2(15)O PET activation. J Neurophysiol 1999;81:1917-26.

29.

Martin RE, Goodyear BG, Gati JS, Menon RS. Cerebral cortical representation of automatic and volitional swallowing in humans. J Neurophysiol 2001;85:938-50.

30.

Cook IJ, Kahrilas PJ. AGA technical review on management of oropharyngeal dysphagia. Gastroenterology 1999;116:455-78.

31.

Holland G, Jayasekeran V, Pendleton N, Horan M, Jones M, Hamdy S. Prevalence and symptom profiling of oropharyngeal dysphagia in a community dwelling of an elderly population: a self-reporting questionnaire survey. Dis Esophagus 2011;24:476-80.

32.

Roy N, Stemple J, Merrill RM, Thomas L. Dysphagia in the elderly: Preliminary evidence of prevalence, risk factors, and

15.

16.

Kinnamon SC. Taste receptor signalling from tongues to lungs. Acta Physiol (Oxf) 2012;204:158-68.

17.

Viana F. Chemosensory Properties of the Trigeminal System. Acs Chemical Neuroscience 2011;2:38-50.

18.

Kitagawa J, Shingai T, Takahashi Y, Yamada Y. Pharyngeal branch of the glossopharyngeal nerve plays a major role in reflex swallowing from the pharynx. Am J Physiol Regul Integr Comp Physiol 2002;282:R1342-R1347.

19.

Hamamoto T, Takumida M, Hirakawa A, Tatsukawa T, Ishibashi T. Localization of transient receptor potential vanilloid (TRPV) in the human larynx. Acta Otolaryngol 2009;129:560-8.

20.

Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389:816-24.

21.

Okumura Y, Narukawa M, Iwasaki Y, Ishikawa A, Matsuda H, Yoshikawa M, et al. Activation of TRPV1 and TRPA1 by Black

- 29 -

Introducción________________________________________ ____________________________ socioemotional effects. Ann Laryngol 2007;116:858-65.

Otol

Rhinol

33.

Bloem BR, Lagaay AM, Vanbeek W, Haan J, Roos RAC, Wintzen AR. Prevalence of Subjective Dysphagia in Community Residents Aged Over 87. BMJ 1990;300:7212.

34.

Kawashima K, Motohashi Y, Fujishima I. Prevalence of dysphagia among communitydwelling elderly individuals as estimated using a questionnaire for dysphagia screening. Dysphagia 2004;19:266-71.

35.

Yang EJ, Kim MH, Lim JY, Paik NJ. Oropharyngeal Dysphagia in a CommunityBased Elderly Cohort: the Korean Longitudinal Study on Health and Aging. J Korean Med Sci 2013;28:1534-9.

36.

Serra-Prat M, Hinojosa G, Lopez D, Juan M, Fabre E, Voss DS, et al. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in independently living older persons. J Am Geriatr Soc 2011;59:1867.

37.

38.

Lee A, Sitoh YY, Lieu PK, Phua SY, Chin JJ. Swallowing impairment and feeding dependency in the hospitalised elderly. Ann Acad Med Singapore 1999;28:371-6. Cabre M, Serra-Prat M, Force L, Almirall J, Palomera E, Clave P. Oropharyngeal Dysphagia is a Risk Factor for Readmission for Pneumonia in the Very Elderly Persons: Observational Prospective Study. J Gerontol A Biol Sci Med Sci 2014;69:330-7.

stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-63. 43.

Kalf JG, de Swart BJM, Bloem BR, Munneke M. Prevalence of oropharyngeal dysphagia in Parkinson's disease: A meta-analysis. Parkinsonism Relat Disord 2012;18:311-5.

44.

Langmore SE, Olney RK, Lomen-Hoerth C, Miller BL. Dysphagia in patients with frontotemporal lobar dementia. Arch Neurol 2007;64:58-62.

45.

Ikeda M, Brown J, Holland AJ, Fukuhara R, Hodges JR. Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer's disease. J Neurol Neurosurg Psychiatry 2002;73:371-6.

46.

Suh MK, Kim HH, Na DL. Dysphagia in Patients With Dementia Alzheimer Versus Vascular. Alzheimer Dis Assoc Disord 2009;23:178-84.

47.

Horner J, Alberts MJ, Dawson DV, Cook GM. Swallowing in Alzheimers-Disease. Alzheimer Dis Assoc Disord 1994;8:177-89.

48.

Nicosia MA, Hind JA, Roecker EB, Carnes M, Doyle J, Dengel GA, et al. Age effects on the temporal evolution of isometric and swallowing pressure. J Gerontol A Biol Sci Med Sci 2000;55:M634-M640.

49.

Robbins J, Hamilton JW, Lof GL, Kempster GB. Oropharyngeal swallowing in normal adults of different ages. Gastroenterology 1992;103:823-9.

39.

Cabre M, Serra-Prat M, Palomera E, Almirall J, Pallares R, Clave P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010;39:39-45.

50.

Aviv JE, Martin JH, Jones ME, Wee TA, Diamond B, Keen MS, et al. Age-related changes in pharyngeal and supraglottic sensation. Ann Otol Rhinol Laryngol 1994;103:749-52.

40.

Nogueira D, Reis E. Swallowing disorders in nursing home residents: how can the problem be explained? Clin Interv Aging 2013;8:221-7.

51.

Aviv JE. Effects of aging on sensitivity of the pharyngeal and supraglottic areas. Am J Med 1997;103:74S-6S.

41.

Lin LC, Wu SC, Chen HS, Wang TG, Chen MY. Prevalence of impaired swallowing in institutionalized older people in taiwan. J Am Geriatr Soc 2002;50:1118-23.

52.

Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146M156.

42.

Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after

53.

Broadley S, Croser D, Cottrell J, Creevy M, Teo E, Yiu D, et al. Predictors of prolonged

- 30 -

Introducción dysphagia following acute stroke. J Clin Neurosci 2003;10:300-5. 54.

55.

56.

57.

58.

59.

60.

61.

62.

Horner J, Buoyer FG, Alberts MJ, Helms MJ. Dysphagia Following Brain-Stem Stroke Clinical Correlates and Outcome. Arch Neurol 1991;48:1170-3. Clave P, de Kraa M, Arreola V, Girvent M, Farre R, Palomera E, et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006;24:1385-94. Aviv JE, Martin JH, Sacco RL, Zagar D, Diamond B, Keen MS, et al. Supraglottic and pharyngeal sensory abnormalities in stroke patients with dysphagia. Ann Otol Rhinol Laryngol 1996;105:92-7. Mann G, Hankey GJ, Cameron D. Swallowing function after stroke - Prognosis and prognostic factors at 6 months. Stroke 1999;30:744-8. Hamdy S, Rothwell JC, Aziz Q, Singh KD, Thompson DG. Long-term reorganization of human motor cortex driven by short-term sensory stimulation. Nat Neurosci 1998;1:648. Belafsky PC, Mouadeb DA, Rees CJ, Pryor JC, Postma GN, Allen J, et al. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol 2008;117:919-24. Wallace KL, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of oral-pharyngeal dysphagia. Gastroenterology 2000;118:678-87. Burgos R, Sarto B, Segurola H, Romagosa A, Puiggros C, Vazquez C, et al. Translation and Validation of the Spanish Version of the Eat10 (Eating Assessment Tool-10) for the Screening of Dysphagia. Nutricion Hospitalaria 2012;27:2048-54. Clave P, Arreola V, Romea M, Medina L, Palomera E, Serra-Prat M. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008;27:806-15.

63.

Suiter DM, Leder SB. Clinical utility of the 3ounce water swallow test. Dysphagia 2008 ;23:244-50.

64.

DePippo KL, Holas MA, Reding MJ. Validation of the 3-oz water swallow test for aspiration following stroke. Arch Neurol 1992 ;49:1259-61.

65.

Rofes L, Arreola V, Clave P. The volumeviscosity swallow test for clinical screening of Dysphagia and aspiration. Nestle Nutr Inst Workshop Ser 2012;72:33-42.

66.

Rosenbek J, Robbins J, Roecker E. A penetration-aspiration scale. Dysphagia 1996;11:93-8.

67.

Leder SB, Murray JT. Fiberoptic Endoscopic Evaluation of Swallowing. Phys Med Rehabil Clin N Am 2008;19:787.

68.

Silva LC, Herbella FAM, Neves LR, Vicentine FPP, Neto SP, Patti MG. Anatomophysiology of the Pharyngo-Upper Esophageal Area in Light of High-Resolution Manometry. J Gastrointest Surg 2013;17:2033-8.

69.

Ferrero I, Ashbaugh R, Arreola V. Cuidados básicos. In: Clave P, Garcia-Peris P, editors. Guía de diagnóstico y de tratamiento nutricional y rehabilitador de la disfagia orofaríngea.Barcelona: Editorial Glosa; 2011.

70.

The British Dietetic Association. Dysphagia Diet Food Texture Descriptors. 2012 [cited 2014 Mar 24]; Available from: URL: http://goo.gl/MQitEO

71.

The National Dysphagia Diet Task Force. National Dysphagia Diet: Standardization for Optimal Care. Chicago: American Dietetic Association; 2002.

72.

Canton A, Valero MA, Alvarez-Hernandez J. Soporte nutricional. In: Clave P, Garcia-Peris P, editors. Guía de diagnóstico y de tratamiento nutricional y rehabilitador de la disfagia orofaríngea. Barcelona: Editorial Glosa; 2011.

73.

Bhattacharyya N, Kotz T, Shapiro J. The effect of bolus consistency on dysphagia in unilateral vocal cord paralysis. Otolaryngol Head Neck Surg 2003;129:632-6.

74.

Groher ME. Bolus Management Aspiration Pneumonia in Patients

- 31 -

and with

Introducción________________________________________ ____________________________ Pseudobulbar 1987;1:215-6. 75.

Dysphagia.

Dysphagia

Dantas RO, Kern MK, Massey BT, Dodds WJ, Kahrilas PJ, Brasseur JG, et al. Effect of Swallowed Bolus Variables on Oral and Pharyngeal Phases of Swallowing. Am J Physiol 1990;258:G675-G681.

84.

Clave P, Arreola V, Velasco M. Tratamiento rehabilitador. In: Clave P, Garcia-Peris P, editors. Guía de diagnóstico y de tratamiento nutricional y rehabilitador de la disfagia orofaríngea.Barcelona: Editorial Glosa; 2011.

85.

Shaker R, Easterling C, Kern M, Nitschke T, Massey B, Daniels S, et al. Rehabilitation of swallowing by exercise in tube-fed patients with pharyngeal dysphagia secondary to abnormal UES opening. Gastroenterology 2002;122:1314-21.

86.

Freed ML, Freed L, Chatburn RL, Christian M. Electrical stimulation for swallowing disorders caused by stroke. Respir Care 2001;46:46674.

87.

Carnaby-Mann GD, Crary MA. Examining the evidence on neuromuscular electrical stimulation for swallowing: a meta-analysis. Arch Otolaryngol Head Neck Surg 2007;133:564-71.

88.

Leelamanit V, Limsakul C, Geater A. Synchronized electrical stimulation in treating pharyngeal dysphagia. Laryngoscope 2002;112:2204-10.

76.

Garcia JM, Chambers E, Molander M. Thickened liquids: Practice patterns of speech-language pathologists. Am J Speech Lang Pathol 2005;14:4-13.

77.

Sura L, Madhavan A, Carnaby G, Crary MA. Dysphagia in the elderly: management and nutritional considerations. Clin Interv Aging 2012;7:287-97.

78.

Shanahan TK, Logemann JA, Rademaker AW, Pauloski BR, Kahrilas PJ. Chin-Down Posture Effect on Aspiration in Dysphagic Patients. Arch Phys Med Rehabil 1993;74:736-9.

79.

Lewin JS, Hebert TM, Putnam JB, Jr., DuBrow RA. Experience with the chin tuck maneuver in postesophagectomy aspirators. Dysphagia 2001;16:216-9. 89.

80.

Rasley A, Logemann JA, Kahrilas PJ, Rademaker AW, Pauloski BR, Dodds WJ. Prevention of barium aspiration during videofluoroscopic swallowing studies: value of change in posture. AJR Am J Roentgenol 1993;160:1005-9.

Blumenfeld L, Hahn Y, Lepage A, Leonard R, Belafsky PC. Transcutaneous electrical stimulation versus traditional dysphagia therapy: a nonconcurrent cohort study. Otolaryngol Head Neck Surg 2006;135:754-7.

90.

Logemann JA, Kahrilas PJ, Kobara M, Vakil NB. The benefit of head rotation on pharyngoesophageal dysphagia. Arch Phys Med Rehabil 1989;70:767-71.

Crary MA, Carnaby-Mann GD, Faunce A. Electrical stimulation therapy for dysphagia: Descriptive results of two surveys. Dysphagia 2007;22:165-73.

91.

Langmore S, Vandaele D, Logemann JA. NMES as a treatment for post-radiated head and neck cancer patients with dysphagia. Dysphagia 2006;21:287-334.

92.

Shaw GY, Sechtem PR, Searl J, Keller K, Rawi TA, Dowdy E. Transcutaneous neuromuscular electrical stimulation (VitalStim) curative therapy for severe dysphagia: Myth or reality? Annals of Otology Rhinology and Laryngology 2007;116:36-44.

93.

Terre R, Valles M, Panades A, Mearin F. Long-lasting effect of a single botulinum toxin injection in the treatment of oropharyngeal dysphagia secondary to upper esophageal sphincter dysfunction: A pilot study. Scand J Gastroenterol 2008;43:1296-303.

81.

82.

83.

Speyer R, Baijens L, Heijnen M, Zwijnenberg I. Effects of therapy in oropharyngeal dysphagia by speech and language therapists: a systematic review. Dysphagia 2010;25:40-65. Ashford J, McCabe D, Wheeler-Hegland K, Frymark T, Mullen R, Musson N, et al. Evidence-based systematic review: Oropharyngeal dysphagia behavioral treatments. Part III-Impact of dysphagia treatments on populations with neurological disorders. J Rehabil Res Dev 2009;46:195204.

- 32 -

Introducción 94.

Carrau RL, Pou A, Eibling DE, Murry T, Ferguson BJ. Laryngeal framework surgery for the management of aspiration. Head Neck 1999;21:139-45.

104. Gallas S, Marie JP, Leroi AM, Verin E. Sensory transcutaneous electrical stimulation improves post-stroke dysphagic patients. Dysphagia 2010;25:291-7.

95.

Logemann JA, Pauloski BR, Colangelo L, Lazarus C, Fujiu M, Kahrilas PJ. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995;38:55663.

105. Baijens LWJ, Speyer R, Passos VL, Pilz W, Roodenburg N, Clave P. The Effect of Surface Electrical Stimulation on Swallowing in Dysphagic Parkinson Patients. Dysphagia 2012;27:528-37.

96.

Pelletier CA, Lawless HT. Effect of citric acid and citric acid-sucrose mixtures on swallowing in neurogenic oropharyngeal dysphagia. Dysphagia 2003;18:231-41.

97.

Ebihara T, Sekizawa K, Nakazawa H, Sasaki H. Capsaicin and swallowing reflex. Lancet 1993;341:432.

98.

Ebihara T, Takahashi H, Ebihara S, Okazaki T, Sasaki T, Watando A, et al. Capsaicin troche for swallowing dysfunction in older people. J Am Geriatr Soc 2005;53:824-8.

99.

Ebihara T, Ebihara S, Maruyama M, Kobayashi M, Itou A, Arai H, et al. A randomized trial of olfactory stimulation using black pepper oil in older people with swallowing dysfunction. J Am Geriatr Soc 2006;54:1401-6.

100. Bulow M, Olsson R, Ekberg O. Videoradiographic analysis of how carbonated thin liquids and thickened liquids affect the physiology of swallowing in subjects with aspiration on thin liquids. Acta Radiol 2003;44:366-72. 101. Ebihara T, Ebihara S, Watando A, Okazaki T, Asada M, Ohrui T, et al. Effects of menthol on the triggering of the swallowing reflex in elderly patients with dysphagia. Br J Clin Pharmacol 2006;62:369-71. 102. Kitagawa J, Nakagawa T, Hasegawa M, Iwakami T, Shingai T, Yamada Y, et al. Facilitation of reflex swallowing from the pharynx and larynx. J Oral Sci 2009;51:16771. 103. Jayasekeran V, Singh S, Tyrrell P, Michou E, Jefferson S, Mistry S, et al. Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions. Gastroenterology 2010;138:1737-46.

106. Kumar S, Wagner CW, Frayne C, Zhu L, Selim M, Feng WW, et al. Noninvasive Brain Stimulation May Improve Stroke-Related Dysphagia A Pilot Study. Stroke 2011;42:1035-40. 107. Shigematsu T, Fujishima I, Ohno K. Transcranial Direct Current Stimulation Improves Swallowing Function in Stroke Patients. Neurorehabil Neural Repair 2013;27:363-9. 108. Yang EJ, Baek SR, Shin J, Lim JY, Jang HJ, Kim YK, et al. Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia. Restor Neurol Neurosci 2012;30:303-11. 109. Rofes L, Vilardell N, Clave P. Post-stroke dysphagia: Progress at last. Neurogastroenterol Motil 2013;25:278-82. 110. Altman KW, Yu GP, Schaefer SD. Consequence of dysphagia in the hospitalized patient: impact on prognosis and hospital resources. Arch Otolaryngol Head Neck Surg 2010;136:784-9. 111. Foley NC, Martin RE, Salter KL, Teasell RW. A Review of the Relationship Between Dysphagia and Malnutrition Following Stroke. J Rehabil Med 2009;41:707-13. 112. Carrion S, Cabré M, Monteis R, Roca M, Palomera E, Serra-Prat M, et al. Oropharyngeal dysphagia is a prevalent risk factor for malnutrition in a cohort of elderly patients admitted with an acute disease to a general hospital. Clin Nutr 2014. In press. 113. Suominen M, Muurinen S, Routasalo P, Soini H, Suur-Uski I, Peiponen A, et al. Malnutrition and associated factors among aged residents in all nursing homes in Helsinki. Eur J Clin Nutr 2005;59:578-83.

- 33 -

Introducción________________________________________ ____________________________ 114. Sheard JM, Ash S, Silburn PA, Kerr GK. Prevalence of malnutrition in Parkinson's disease: a systematic review. Nutr Rev 2011;69:520-32. 115. Resolution ResAP(2003)3 on food and nutritional care in hospitals. Council of Europe, Comitte of Ministers. 2003 [cited 2014 Mar 24]; Available from: URL: http://goo.gl/6Amw2z 116. Vellas B, Guigoz Y, Garry PJ, Nourhashemi F, Bennahum D, Lauque S, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition 2009;15:116-22. 117. Kaiser MJ, Bauer JM, Ramsch C, Uter W, Guigoz Y, Cederholm T, et al. Validation of the Mini Nutritional Assessment short-form (MNA-SF): A practical tool for identification of nutritional status. J Nutr Health Aging 2009;13:782-8. 118. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M. ESPEN guidelines for nutrition screening 2002. Clin Nutr 2003;22:415-21. 119. Marik PE, Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest 2003;124:328-36. 120. Silver FL, Norris JW, Lewis AJ, Hachinski VC. Early Mortality Following Stroke - A Prospective Review. Stroke 1984;15:492-6.

121. Vermeij FH, Reimer WJMS, de Man P, van Oostenbrugge RJ, Franke CL, de Jong G, et al. Stroke-Associated Infection Is an Independent Risk Factor for Poor Outcome after Acute Ischemic Stroke: Data from the Netherlands Stroke Survey. Cerebrovasc Dis 2009;27:465-71. 122. Beyer MK, Herlofson K, Arsland D, Larsen JP. Causes of death in a community-based study of Parkinson's disease. Acta Neurol Scand 2001;103:7-11. 123. Teramoto S, Fukuchi Y, Sasaki H, Sato K, Sekizawa K, Matsuse T. High incidence of aspiration pneumonia in community- and hospital-acquired pneumonia in hospitalized patients: A multicenter, prospective study in Japan. J Am Geriatr Soc 2008;56:577-9. 124. Jackson ML, Nelson JC, Jackson LA. Risk Factors for Community-Acquired Pneumonia in Immunocompetent Seniors. J Am Geriatr Soc 2009;57:882-8. 125. Loeb M, Neupane B, Walter SD, Hanning R, Carusone SC, Lewis D, et al. Environmental Risk Factors for Community-Acquired Pneumonia Hospitalization in Older Adults. J Am Geriatr Soc 2009;57:1036-40. 126. Koivula I, Sten M, Makela PH. Risk-Factors for Pneumonia in the Elderly. Am J Med 1994;96:313-20.

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HIPÓTESIS Y OBJETIVOS

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Hipótesis y Objetivos HIPÓTESIS 1. La disfagia orofaríngea (DO) puede ser detectada clínicamente con una alta sensibilidad y especificidad mediante métodos de cribado y de exploración en la cabecera del paciente. El cuestionario EAT-10 y el método de exploración clínica de la deglución volumen-viscosidad (MECV-V) cumplen las características psicométricas necesarias para ser ser usados como métodos de cribado y de evaluación clínica para la DO respectivamente. 2. El estudio mediante videofluoroscopia del patrón deglutorio de los ancianos frágiles y de los ancianos con neumonía adquirida en la comunidad nos puede permitir identificar aquellos eventos fisiopatológicos críticos, que conducen a la alteración de la seguridad y de la eficacia de la deglución en estos fenotipos de pacientes ancianos. 3. La DO es un factor de riesgo para el desarrollo de neumonía adquirida en la comunidad en ancianos, y un factor de mal pronóstico clínico en ancianos frágiles y con neumonía adquirida en la comunidad. 4. El incremento de la viscosidad del bolo mediante espesantes previene las aspiraciones en pacientes con DO sin modificar la respuesta motora orofaríngea; los espesantes de goma xantana presentan un mejor perfil terapéutico que los de almidón. 5. Los receptores TRP pueden ser una nueva diana farmacológica para el tratamiento de la DO. La suplementación del bolo alimentario con agonistas de los receptores TRP aumenta el input sensorial hacia los centros deglutorios corticales y sub-corticales, facilitando el cierre del vestíbulo laríngeo, mejorando la respuesta motora orofaríngea y evitando las aspiraciones. 6. La estimulación eléctrica transcutánea es un tratamiento seguro y eficaz para la DO post-ictus. El efecto terapéutico de la estimulación eléctrica transcutánea se debe no solo a su efecto sobre los músculos efectores, sino que la integración sensorial del estímulo eléctrico es también en parte responsable del efecto observado.

OBJETIVOS 1. Determinar las características psicométricas y la validez de un método de cribado (EAT-10) y un método de evaluación clínica (MECV-V) para detectar la presencia de disfagia orofaríngea (DO). 2. Caracterizar la fisopatología de la DO y el patrón deglutorio de dos fenotipos de pacientes ancianos (>70 años) con disfagia orofaríngea: el anciano frágil y el anciano con neumonía adquirida en la comunidad. Determinar si la disfagia orofaríngea es un factor de riesgo de neumonía adquirida en la comunidad en el anciano y su impacto como factor pronóstico en pacientes ancianos frágiles y en ancianos con neumonía adquirida en la comunidad. 3. Evaluar el efecto terapéutico y el mecanismo de acción de tres tipos de estrategias terapéuticas para los pacientes con DO asociada al envejecimiento y a enfermedades neurológicas: a) Tratamiento compensador mediante espesantes: derivados del almidón y goma xantana. b) Tratamiento de neuro-estimulación farmacológica mediante la adición al bolo alimentario de agonistas de los Transient Receptor Potential Channels (TRP): capsaicina y piperina. c) Tratamiento de rehabilitación mediante dos transcutánea a intensidad sensorial y motora.

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protocolos

de

estimulación

eléctrica

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CAPÍTULO 1

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Screening for oropharyngeal dysphagia

Capítulo 1 SENSITIVITY AND SPECIFICITY OF THE EATING ASSESSMENT TOOL AND THE VOLUME-VISCOSITY SWALLOW TEST FOR CLINICAL EVALUATION OF OROPHARYNGEAL DYSPHAGIA Laia Rofes, Viridiana Arreola, Rajat Mukherjee, Pere Clavé. Sensitivity and specificity of the Eating Assess¬ment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia. Under review in

Neurogastroenterol Motil (accepted with Major Revision).

Abstract Background: Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. Methods: We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, residue) and impaired safety of swallow (cough, voice changes, oxygen desaturation≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. Results: According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety and 0.91 sensitivity and 0.28 specificity for aspirations. Conclusions: Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia.

Introduction Oropharyngeal dysphagia (OD) is a gastrointestinal motility disorder that includes difficulty or inability to form or move the alimentary bolus safely from the mouth to the oesophagus and that can include tracheobronchial aspirations.[1] OD is a highly prevalent condition in 37-78% of patients after a stroke[2] and 23-47.5% of different phenotypes of elderly people.[3;4] It is specifically classified as a digestive condition by the World Health Organization in the International Statistical Classification of Diseases and Related Health Problems ICD-9 and ICD-10.[5] OD is one of the major contributors to malnutrition[6], a highly

prevalent condition among hospital patients that leads to extended hospital stays, prolonged rehabilitation, and diminished quality of life.[4] OD can also lead to respiratory infections and aspiration pneumonia with an associated mortality of up to 50%.[7] Despite its high prevalence and severe complications, OD is not always systematically explored and detected, and most patients are not even diagnosed and do not receive any treatment for this condition. Videofluoroscopy (VFS) is the gold standard to study oral and pharyngeal mechanisms of OD, swallowing dysfunction and aspiration.[1] However, it is not feasible to perform a VFS on every patient at risk for OD as it requires specific equipment not

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Capítulo 1___________________________________________________________________ available in all healthcare facilities. Therefore, the development of clinical methods for easy screening and accurate clinical assessment of OD is necessary. The goal of the screening methods for OD should be quick identification of patients with OD, at risk of aspiration or malnutrition, and who need to be referred for more formal and extensive swallowing assessment. One such screening tool is the Eating Assessment Tool (EAT-10), a 10-item self-administered questionnaire developed to evaluate dysphagia symptoms in persons with a wide variety of causes of dysphagia and in different clinical settings.[8;9] However, these studies were not done against a gold standard and the diagnostic accuracy of the EAT-10 as an OD screening tool has not been established. The goal of the clinical assessment methods for OD should be, in addition to collecting the data necessary to establish a clinical diagnosis, to assess the pathophysiology of the disease, to identify the main signs and symptoms of OD and the mechanism of swallowing dysfunction, and to help to select the most appropriate therapy for those patients (such as elderly patients admitted to nursing homes) who cannot easily undergo VFS. A recent systematic review recommended bedside clinical tests using water or other fluids combined with oximetry, the endpoints being coughing, choking, voice changes and desaturation to identify patients with OD.[10] The volume-viscosity swallow test (V-VST) fulfils these criteria and shows high diagnostic accuracy in identifying clinical signs and symptoms of impaired efficacy and safety of swallow.[11] In addition, the V-VST establishes the ideal viscosity to be safely administered to patients at risk of OD and aspirations. The V-VST was first validated against VFS by using liquids thickened with a starch-based thickener [12], however the diagnostic accuracy of the V-VST using the new generation of thickeners based on xanthan-gum has not been established. It is relevant to do so, as the rheological properties of liquids thickened with xanthan gum differ from those of liquids thickened with starch.[13] The inter-rater reliability of the V-VST also needs to be addressed. The aim of the present study was to validate the screening method EAT-10 and the clinical bedside assessment method V-VST in the detection of OD.

Materials and Methods Subjects A stratified-sampling design was chosen for the study, using the data from previous studies to estimate OD prevalence and sub-population proportions.[12] Based on this sampling method, data were simulated from the data available using re-sampling techniques.[12] Boot-strapped confidence intervals were then obtained for different sample sizes using the beta-binomial model suggested for the primary analysis. A sample size of 134 (120 at-risk patients and 14 healthy volunteers) was chosen to estimate the sensitivities with 10% margin of error (length of the 95% simultaneous confidence intervals would be at most 20%). This ensured that the margin of errors for estimating the specificities was at most 15%. Thus, one hundred twenty patients with a history of swallowing difficulties associated with aging, stroke and neurodegenerative diseases consecutively referred to the Gastrointestinal Physiology Lab of the Hospital de Mataró (Spain) for swallowing evaluation and 14 adult healthy volunteers (>18 years), were prospectively included in the study between June 2010 and June 2011. The study protocol was approved by the Institutional Review Board of the Hospital de Mataró and was conducted according to the principles and rules laid down in the Declaration of Helsinki and its subsequent amendments. Trial registration: NCT01158313.

Design Oropharyngeal dysphagia was clinically evaluated in all patients and controls by means of a screening questionnaire, the EAT-10[8] and a clinical bedside assessment method, the V-VST.[12] Each test was performed by an independent clinician. The same day, a VFS was also performed on all subjects by a clinician blinded to the results of all clinical evaluations. The results from the VFS are considered as the reference standard for establishing the disease status (presence of OD) and characteristics of swallowing dysfunction (impaired safety and/ or efficacy of deglutition). Following the videofluoroscopic study, a second VVST was performed by another clinician, blinded to the results of the EAT-10, the first V-VST and the

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Screening for oropharyngeal dysphagia VFS, to assess its test-retest reliability. In addition, socio-demographic, clinical and nutritional parameters were collected for all participants.

Index tests 1) The Eating Assessment Tool (EAT-10): The 10-item Spanish-language-validated version of the screening questionnaire EAT-10[9] was administered to all patients and healthy volunteers. Patients were instructed to complete the EAT-10 by themselves but could have guidance by relatives or caregivers if needed. The EAT-10 consists of 10 questions about the severity of symptoms of OD and its clinical and social impact, each question scoring from 0 (no problem) to 4 (severe problem). Normative data from previous studies explored the upper limit of reference interval and suggested that a final EAT-10 score ≥3 was abnormal.[8] 2) The Volume-Viscosity Swallow Test (V-VST): The V-VST method was performed as described previously.[14] Briefly, the patients’ ability to swallow boluses of different volumes (5, 10 and 20 mL) and viscosities (nectar-like, thin liquid, extremespoon thick (EST)) was evaluated following the algorithm in Figure 1. Signs of impaired efficacy of swallow, such as impaired labial seal, oral residue, piecemeal deglutition (multiple swallows per bolus) and symptoms of pharyngeal residue (auto-reported by the patient as the feeling of having the bolus stuck in the throat after the deglutition), and signs of impaired safety of swallow such as changes in voice quality (including wet voice), cough and decrease in oxygen saturation ≥3% (measured with a finger pulse-oximeter, Nellcor™ OxiMax™, Philips Medical Systems, Eindhoven, Netherlands) were evaluated for each patient. A patient who presented one or more signs of impaired efficacy and/or safety of swallow was considered as having oropharyngeal dysphagia. All clinical explorations, including oxygen saturation measurements, were filmed with a digital video camera (DVR-PC100E, Mini DV, Sony Corporation, Tokyo, Japan) to allow study traceability.

Reference test Videofluoroscopy: All patients were imaged for the videofluoroscopic study while seated, in a lateral projection which included the oral cavity, pharynx,

larynx, and cervical oesophagus. Videofluoroscopic recordings were obtained by using a Super XT-20 Toshiba Intensifier (Toshiba Medical Systems Europe, Zoetermeer, The Netherlands) and recorded at 25 frames/s using a Panasonic AG DVX-100B video camera (Matsushita Electric Industrial Co, Osaka, Japan). Digitization, analysis and measurements of videofluoroscopic images were made using the software Swallowing Observer (Image and Physiology SL, Barcelona, Spain). The ability of the patients to swallow boluses of different volumes and viscosities was also evaluated following the same strategy as in the clinical assessment by the V-VST (Figure 1). An impairment of the efficacy of swallow was considered when at least one of the following signs was identified during the videofluoroscopic study: impaired labial seal closure, oral residue, pharyngeal residue or piecemeal deglutition; and an impairment of the safety of swallow was considered when a penetration or an aspiration was detected. The penetrations and aspirations were classified according to the penetration-aspiration scale.[15] A patient who presented an impairment of the efficacy and/or the safety of swallow was considered as having oropharyngeal dysphagia.

Bolus viscosities Three different viscosities (thin liquid, nectar-like and EST) were used during V-VST and VFS according to the viscosity ranges of the National Dysphagia Diet Task Force, which are 1-50 mPas for liquids, 51-350 mPas for nectar-like and >1750 mPas for EST.[16]. For V-VST studies, thin viscosity was obtained by using mineral water at room temperature, nectar-like viscosity by adding 1.2 g of thickener (Resource ThickenUp Clear, Nestlé Health Science, Lausanne, Switzerland) to 100 mL mineral water, and EST viscosity by adding 6 g of thickener to 100 mL mineral water. Solutions were prepared 5 min before the test. According to the study protocol, the specific levels of viscosity obtained were 21 mPa s for thin liquids, 238 mPa s for nectar, and 1840 mPa s for EST.[14] For VFS studies, the X-ray contrast Gastrografin (Bayer Hispania SL, Sant Joan Despí, Spain) was diluted 1:1 in mineral water, both at room temperature, to obtain the thin viscosity.

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Capítulo 1___________________________________________________________________ Dilution avoids any potential damage to lung tissue in case of aspiration. For thickened solutions, the amount of thickener was adjusted to account for the effect of the X-ray contrast in order to obtain equivalent viscosities to those used in the V-VST. Nectar viscosity was obtained by adding 2.4 g of the thickener to the thin liquid solution containing the Xray contrast and EST viscosity by adding 5.4 g of the thickener. The solutions for VFS studies were prepared 3 hours prior to the videofluoroscopic examination, in order to obtain stable and equivalent viscosities to those used during the VVST.[13] Boluses of 5 mL, 10 mL and 20 mL of each viscosity were carefully placed in the anterior part of the mouth with a syringe to ensure accurate measurement of bolus volume during both V-VST and VFS studies.

Post-test probabilities To assess the probability of presenting OD in the target populations after the test result, positive and negative predictive values (PPV and NPV) of EAT10 and V-VST were assessed for independentlyliving and institutionalized elderly people respectively. In our population, pre-test probability (prevalence of OD) for independently-living elderly people is 23%[3] and for institutionalized elderly people, 47.5%.[4]

Data analysis and statistical methods

Figure 1. V-VST algorithm. Patients with safe swallow started the exploration with a 5 mL nectar bolus, followed by 10 mL and 20 mL nectar boluses, then performed the thin liquid series with boluses of increasing volume and finally completed the pathway with the three EST boluses to explore efficacy of swallow. If the patient presented signs of impaired safety at nectar or thin liquid viscosities, the series was interrupted and the EST series was assessed. EST, extreme spoon-thick.

Quantitative parameters were described by mean±SD and qualitative parameters were described by relative and absolute frequencies. To assess the diagnostic accuracy of the EAT-10 relative to VFS, a receiver operating characteristic (ROC) curve was created plotting sensitivity versus 1-specificity values for each possible cut-off and calculating the area under the curve (AUC). Sensitivity and specificity of the V-VST relative to the videofluoroscopy for dysphagia, impaired safety and impaired efficacy were measured using a conditional likelihood approach and expressed as mean and 95% confidence intervals (CI). The BetaBinomial model was used to model the three binary outcomes (dysphagia, impaired safety and impaired efficacy) with specific covariates comprising the corresponding videofluoroscopic

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Screening for oropharyngeal dysphagia result.[17] As the V-VST for each subject was performed twice by independent blinded readers, a subject-specific random-effect term was added to the Beta-Binomial model to obtain a mixed-effect model. PPV and NPV were also assessed, taking the mixed-beta binomial estimates for sensitivities and specificities and the prevalence of the particular impairment. The Bayes’ theorem was used to compute the PPV and NPV from estimates of the test’s sensitivity and specificity and pre-test probabilities of OD in the target populations. Using the Beta-Binomial model, simultaneous confidence intervals for sensitivity and specificity for several parameters were obtained, accounting for the multiplicity. The inter-rater agreement for V-VST in the diagnosis of dysphagia was estimated by means of the Cohen’s Kappa coefficient. Statistical analysis was performed using the stats package in R version 2.15 (www.r-project.org). The package bbmle was used to obtain the maximum likelihood estimates for the beta-binomial parameters.

Results Subjects A total of 134 participants were included in the study. Demographic, clinical and nutritional characteristics of the study population are described in Table 1. It is worth noting that most patients included in the study presented advanced age (74.4±12.4 years), polymorbidity (Charlson Comorbidity Index 3.04±1.92), high risk of malnutrition (Mini Nutritional Assessment short form, MNA-SF 9.72±2.76) and polymedication (7.77±3.7 drugs/ patient). Patients taking drugs with potential effects on swallow function were: 33.3%, antidepressants; 24.8%, anxiolytics; 16.2%, antiepileptics; 8.5%, sedatives and 4.3%, antipsychotics. One patient presented a serious adverse event during the study with a severe aspiration during the V-VST resulting in tachycardia. The patient was withdrawn from the study and recovered after a few hours. A second subject wished to withdraw before the study end and a third subject could not be analyzed because the VFS images were damaged.

Table 1. Demographic, clinical and nutritional characteristics of the study population. Healthy volunteers (HV); neurodegenerative disease (NDD); Mini Nutritional Assessment short form (MNA-SF)

Patients HV

Patients

14

Sex (men) Age (years)

NDD

Stroke

Elderly

120

10.8% (13)

55% (66)

34.2% (41)

57.1% (8)

54.2% (65)

46.2% (6)

56.1% (37)

53.7% (22)

30.5±6.1

74.4±12.4

64.0±19.6

73.5±11.4

79.6±8.2

100% (14)

10.1% (12)

17.5% (7)

0.0% (0)

38.5% (5)

1-2

0% (0)

31.1% (37)

40.0% (16)

25.8% (17)

30.8% (4)

3-4

0% (0)

37.0% (44)

35.0% (14)

39.4% (26)

30.8% (4)

≥5

0% (0)

21.8% (26)

7.5% (3)

34.8% (23)

0.0% (0)

Malnourished (0-7)

22.9%(27)

23.1% (3)

25.8% (17)

17.9% (7)

At risk (8-11)

48.3% (57)

38.5% (5)

53.0% (35)

43.6% (17)

Well nourished (12-14)

28.8% (34)

38.5% (5)

21.2% (14)

38.5% (15)

Subjects

Charlson Index 0

Nutritional status (MNA-SF)

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Capítulo 1___________________________________________________________________

Reference Test Results Videofluoroscopy. Videofluoroscopic images for analysis were available from 131 subjects. Prevalence of OD according to the VFS study was 87% (114) of the included subjects, 75.6% (99) of them presenting VFS signs of impaired efficacy and 80.9% (106) signs of impaired safety of swallow. Efficacy signs: impaired labial seal closure was observed in 6.1% (8) of subjects, piecemeal deglutition in 68.7% (90), oral residue in 31.3% (41) and pharyngeal residue in 27.5% (36). Safety signs: According to the penetration-aspiration scale,[14] 30.5% (40) of subjects presented score 2 penetrations (material enters the airway, remains above the vocal folds, and is ejected from the airway), 32.1% (42) scores 3-5, (severe penetrations into the laryngeal vestibule not ejected from the airway and/or contacting the vocal folds ) and 18.3% (24) scores 6-8 (aspirations into the

airway), 62.5% (15) of which were silent (score 8). Increasing bolus viscosity improved the safety of swallow of 80.9% (106) of subjects.

Index Test Results 1) EAT-10: The median EAT-10 score of the subjects included in the study was 9 with 25-75 percentiles of 3-16. The score of healthy subjects was 0, that of patients with swallowing complaints but normal videofluoroscopy results, 3 (1-11.5) and the median score of patients diagnosed with OD was 10 (4-16) (P<0.001). Patients with impaired efficacy of swallow presented a median EAT-10 of 11 with 25-75 percentiles of 5-16 and patients with impaired safety 11 (4-16). Up to 75.9% (101) of the 133 subjects that completed the EAT-10 presented a score above the upper limit of the reference interval (≥3) (Figure 2).

Figure 2. Flow chart of subjects included in the study that underwent the EAT-10. Subjects stratified by presence of oropharyngeal dysphagia according to the VFS study.

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Screening for oropharyngeal dysphagia 2) V-VST: 78.4% (105) of subjects included in the study presented OD according to the V-VST, 58.2% (78) of them presenting signs of impaired efficacy of swallow and 73.1% (98) presenting signs of impaired safety (Figure 3). According to the V-VST, increasing bolus viscosity with thickener improved the safety of swallow of 72.4% (97) subjects and the efficacy of swallow of 1 subject.

Accuracy of the EAT-10 and V-VST for detecting OD 1) EAT-10: The AUC of the ROC curve for detecting OD was 0.89 (95% CI=0.802-0.988); for detecting impaired safety, 0.82 (95% CI=0.7190.928) and for detecting impaired efficacy, 0.79

(95% CI=0.682-0.890). The discriminating ability of the EAT-10 for the normative cut-off value (EAT10≥3) to detect dysphagia, impaired efficacy, impaired safety of swallow and aspirations is shown in Table 2. According to the ROC curve, the optimal cut-off to detect dysphagia [0.895 (95% CI=0.8230.944) sensitivity and 0.824 (95% CI=0.566-0.962) specificity], impaired safety of swallow [0.915 (95% CI=0.845-0.960) sensitivity and 0.680 (95% CI=0.465-0.850) specificity] and silent aspirations [0.933 (95% CI=0.680-0.998) sensitivity and 0.215 (95% CI =0.145-0.301) specificity] was 2, and to detect impaired efficacy of swallow was 4 [0.859 (95% CI=0.774-0.920) sensitivity and 0.719 (95% CI=0.532-0.862) specificity] (Figure 4).

Figure 3. Flow chart of subjects included in the study that underwent the first V-VST. A) Subjects stratified by presence of oropharyngeal dysphagia according to the VFS study; B) Subjects stratified by presence of signs of impaired safety of swallow (penetrations, aspirations and safe swallow) according to the VFS study. Note that the test was performed twice, to calculate sensitivity and specificity values of the V-VST, so a subject-specific random-effect term was added to the beta-binomial model to obtain the mixed-effect model.

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Capítulo 1___________________________________________________________________ Table 2. Accuracy of the EAT-10 in detecting dysphagia, impaired efficacy and safety of swallow and aspirations at the normative cutoff 3. CI, simultaneous confidence interval; PPV, positive predictive value; NPV, negative predictive value; OD, oropharyngeal dysphagia.

EAT-10 ≥3 Sensitivity (95% CI)

Specificity (95% CI)

PPV

NPV

LHR+

LHR-

OD

0.85 (0.77-0.91)

0.82 (0.57-0.96)

0.828

0.847

4.72

0.183

Impaired efficacy

0.88 (0.80-0.94)

0.59 (0.41-0.76)

0.684

0.830

2.15

0.203

Impaired safety Aspirations

0.87 (0.79-0.93)

0.68 (0.46-0.85)

0.731

0.837

3.13

0.191

0.83 (0.61-0.95)

0.25 (0.17-0.34)

0.525

0.592

1.11

0.680

Figure 4. ROC curves of EAT-10 to detect dysphagia, impaired efficacy and impaired safety of swallow with respect to VFS findings.

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Screening for oropharyngeal dysphagia Table 3. Accuracy of the V-VST to detect dysphagia, impaired efficacy and safety of swallow and aspirations. CI, simultaneous confidence interval; PPV, positive predictive value; NPV, negative predictive value; OD, oropharyngeal dysphagia.

V-VST Sensitivity (95% CI)

Specificity (95% CI)

PPV

NPV

LHR+

LHR-

OD

0.94 (0.87-0.98)

0.88 (0.50-0.99)

0.98

0.70

7.83

0.068

Impaired efficacy

0.79 (0.62-0.90)

0.75 (0.45-0.92)

0.93

0.67

3.16

0.280

Impaired safety

0.87 (0.74-0.94)

0.81 (0.48-0.95)

0.93

0.46

4.58

0.160

0.91 (0.78-0.99)

0.28 (0.17-0.34)

0.21

0.94

1.26

0.321

Aspirations

2) V-VST: The discriminating ability of the V-VST (sensitivity, specificity and predictive values) for dysphagia, impaired efficacy and safety of swallow and aspirations is shown in Table 3. Interestingly, any sign of impaired safety of swallow in the VVST predicts the presence of silent aspirations with a sensitivity of 1.00 (95% CI=0.782-1.00) and a specificity of 0.320 (95% CI=0.220-0.394). Moreover, the V-VST showed a sensitivity of 0.821 (95% CI =0.734-0.888) and a specificity of 0.640 (95% CI=0.425-0.820) in detecting patients whose swallow improved with the enhancement of bolus viscosity.

(V-VST) of OD offer high discriminating ability. We also found that OD was a serious condition characterized by impairment in oropharyngeal function including frequent silent aspirations, and occurred in vulnerable patients at risk of severe nutritional and respiratory complications. Following these results, we recommend the universal application of these methods among older and neurological patients at risk for OD and nutritional or respiratory complications to identify those that could need a more exhaustive evaluation by instrumental techniques. OD is a prevalent and severe gastrointestinal motility disorder with a very poor prognosis, but the implementation of structured dysphagia programs in hospital settings that systematically evaluate and treat OD reduce the incidence of pneumonia, costs for antibiotics and mortality rates.[18;19] However, despite the high prevalence, morbidity, mortality and costs caused by nutritional and respiratory complications, OD is mostly underdiagnosed and undertreated even in tertiary clinical settings providing specialized care of older adults. The low level of awareness among healthcare professionals and the lack of validated and feasible clinical tools for bedside screening and assessment of OD contribute to this situation. In the present study, we provide validated clinical tools to remedy it.

Post-test probabilities PPV and NPV of OD for EAT-10 in independently living elderly people were 0.603 and 0.963 respectively. For the V-VST in institutionalized elderly people, the PPV and NPV of OD were 0.876 and 0.942 respectively.

Inter-rater correlation for V-VST The V-VST showed a good inter-rater agreement for detecting dysphagia with a Kappa coefficient of 0.628 (95% CI=0.45-0.78).

Discussion

The studied population presented many comorbidities, low functionality, impaired nutritional status and high prevalence of OD, most of them

The main conclusion of this study is that clinical methods for screening (EAT-10) and assessment

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Capítulo 1___________________________________________________________________ dependent on disease prevalence and indicate the probability of having the disease following the test, helping the clinician decide how to manage and treat the patient according to the result of the diagnostic test. Following these results we recommend the EAT-10 as a first-line tool for systematic screening of at-risk patients, especially in primary care settings, as it is easy and accurate, facilitating its use to general practitioners and allied healthcare professionals not specifically trained in OD. We believe that patients with an EAT-10 ≥2 should be considered for further clinical bedside assessment.

presenting signs of both impaired efficacy and safety of swallow. Prevalence of silent aspirations in the studied population was high (11.4%). This is a serious finding that, taken together with the poor health status and high prevalence of malnutrition, put our population at high risk for severe complications including aspiration pneumonia and death.[7;20] Screening for OD should be an easy, quick and low cost process able to detect the majority of patients with the disease. At this stage of the diagnostic process, high sensitivity is more desirable than high specificity, as the cost of a more exhaustive swallowing evaluation is preferable to the potentially fatal complications of undetected dysphagia. The 10-item selfadministered questionnaire EAT-10 includes questions about dysphagia symptoms in patients with swallowing disorders. In its initial validation study, Belafsky et al found EAT-10 displayed excellent internal consistency, good reproducibility and criterion-based validity and suggested that an EAT-10 score of 3 or higher should be considered abnormal. The score 3 was obtained from the upper limit of reference interval (mean+2SD) of the healthy volunteers score. However, the drawback is that the upper limit found for negative (healthy) subjects overlaps with the lower limit found for positive (diseased) cases, leading to the misclassification of some dysphagic patients as negatives. According to the results of our ROC curve, reducing the cut-off from 3 to 2 increased the sensitivity of the test nearly 5% without affecting the specificity, resulting in fewer false negative cases. To the author’s knowledge, the accuracy of only one other questionnaire (the Swallowing Disturbance Questionnaire)[21] has been previously assessed, using FEES as a reference test, and it presented lower sensitivity and specificity values (71.88% and 78.38% respectively) than the EAT-10. In addition, posttest probabilities (PPV and NPV) of EAT-10 for OD in independently-living elderly people were calculated considering the true prevalence of OD in this population (23%)[3], further confirming the low probability of presenting OD after a negative test (EAT-10 <2). Sensitivity and specificity are intrinsic properties of each diagnostic test, independent of disease prevalence. In contrast, PPV and NPV are

The clinical bedside tests for swallowing assessment of OD should present good psychometric properties, good reliability, a detailed and easy-to-perform protocol designed to protect patients’ safety and able to evaluate the safety and efficacy of swallowing, and a system to detect silent aspirations. The V-VST is an accurate bedside assessment method that was designed for this purpose.[12] The V-VST should be administered by trained healthcare professionals at all medical facilities and can be repeated according to the natural progression of the disease. The test presented high diagnostic sensitivity and high positive predictive value to detect OD, impaired safety and aspirations (including silent aspirations), clearly showing a high discriminating ability. Nevertheless, the specificity for detecting aspirations is low (the test is not able to clearly differentiate between aspirations and penetrations and an instrumental study is needed to discriminate between the two impaired safety signs). However, penetrations scoring 3 or higher in the PAS are also a clinically-significant sign of impaired safety of swallow that puts patients at risk of pneumonia.[22] Therefore, the high positive predictive value of the V-VST for impaired safety (penetrations or aspirations) permits the accurate selection of these patients at risk of respiratory complications and the high negative predictive value for aspiration rules out aspiration in a patient with a negative V-VST (post-test probability of 6%). Moreover, the V-VST characterizes the pathophysiology of the impaired swallow function by identifying impaired safety or efficacy of swallow and also detects patients who improve with thickener treatment. In addition, the V-VST

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Screening for oropharyngeal dysphagia levels of thickened liquids for patients with dysphagia.

establishes the ideal viscosity to safely administer to patients at risk of aspirations, adding value to its diagnostic capacity. In a systematic review, Bours and colleagues[10] recommend a water test combined with oximetry using coughing, choking and voice alteration as the endpoints as the best method to clinically assess patients for OD. The water tests are one of the most extended and frequently used tests for dysphagia screening. They present a sensitivity of 51-85% and a specificity of 66-75% to detect aspirations, and a sensitivity of 27-79% and specificity of 63-88% to detect impaired safety of swallow (penetrations or aspirations).[23-26] These parameters are inferior to those offered by the V-VST in the present study. Moreover, the water tests involve the continuous swallow of large amounts of water which may place the patient at risk for aspiration, can miss silent aspirations if oxygen saturation is not monitored [27;28] and do not assess any parameter related to the efficacy of swallow (residue) nor evaluate the ability of patients to swallow different viscosities. Like the V-VST, several tests have been developed using different viscosities and solids to evaluate aspiration and/or penetration. Sensitivity of these tests range from 41% to 100% and specificity from 57% to 82%.[2931] Although these tests evaluate patients’ ability to swallow material of different consistencies, they are not combined with oxygen desaturation, and therefore silent aspirations can be underdiagnosed. Smith et al[32] recommended a water test combined with oxygen saturation followed by bedside swallowing assessment with a variety of quantities and consistencies. This protocol showed a sensitivity of 80% and specificity of 68% for OD, but did not provide a detailed protocol for the swallow test and only acute poststroke patients were studied. Following these results, we recommend the V-VST for systematic bedside clinical assessment of swallowing function of high risk populations, such as elderly patients admitted to general hospitals, nursing home residents and patients with neurological diseases. The V-VST should be performed by trained healthcare professionals. We would like to emphasize that in this study the viscosities used in the VFS perfectly matched those used in the VVST and so can be used to prescribe the different

Differences in ages between the control and patient groups may constitute a limitation of this study because it affects blinding and may influence the researcher’s response or diagnosis. Although VFS interpretations were not specifically assessed for reliability in this study, internal controls of our unit found good intra-rater and inter-rater reliability for identification of aspiration and assessment of the Penetration-Aspiration Scale. Similar results were reported in previous studies when the VFS analyses were made by trained clinicians, as they were in our study [33;34]. In conclusion, our study shows that the discriminating ability of both the EAT-10 questionnaire for clinical screening of OD and the V-VST for clinical bedside assessment is very high and both are useful methods for detecting patients at risk for nutritional and respiratory complications who need more exhaustive instrumental evaluation. We recommend their universal application for populations at risk of OD to ensure comprehensive dysphagia care, to avoid the serious nutritional and respiratory complications associated with OD, to reduce the mortality rates and the economic and social burden associated with this disease and to improve quality of life of dysphagic patients.

References

- 51 -

1.

Cook IJ, Kahrilas PJ. AGA technical review on management of oropharyngeal dysphagia. Gastroenterology 1999;116:45578.

2.

Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-63.

3.

Serra-Prat M, Hinojosa G, Lopez D, Juan M, Fabré E, Voss DS, Calvo M, Marta V et al. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in independently living older persons. J Am Geriatr Soc 2011;59:186-7.

4.

Cabré M, Serra-Prat M, Force Ll, Almirall J, Palomera E, Clavé P. Oropharyngeal

Capítulo 1___________________________________________________________________ dysphagia is a risk factor for readmission for pneumonia in the very elderly: observational prospective study. J Gerontol A Biol Sci Med Sci 2013; in press (doi: 10.1093/gerona/glt099) 5.

World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision. 2010. http://goo.gl/Hw82W (accessed 16 Nov 2012).

6.

Council of Europe, Committee of Ministers. Resolution ResAP(2003)3 on food and nutritional care in hospitals. http://goo.gl/Lmb7E (accessed 16 Nov 2012).

7.

Cabre M, Serra-Prat M, Palomera E, Almirall J, Pallares R, Clavé P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010;39:39-45.

8.

Belafsky PC, Mouadeb DA, Rees CJ, Pryor JC, Postma GN, Allen J, Leonard RJ. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol 2008;117:919-24.

9.

Burgos R, Sarto B, Segurola H, Romagosa A, Puiggrós C, Vázquez C, Cárdenas G, Barcons N, et al. Traducción y validación de la versión en español de la escala EAT-10 (Eating Assessment Tool-10) para despistaje de la disfagia. Nutr Hosp 2012;27:20482054.

10.

Connolly MJ. Of proverbs and prevention: aspiration and its consequences in older patients. Age Ageing 2010;39:2-4.

11.

Bours GJ, Speyer R, Lemmens J, Limburg M, de Wit R.. Bedside screening tests vs. videofluoroscopy or fibreoptic endoscopic evaluation of swallowing to detect dysphagia in patients with neurological disorders: systematic review. J Adv Nurs 2009;65:47793.

12.

13.

properties of videofluoroscopic contrast agents and thickened liquid prescriptions. Dysphagia. Published Online First: 14 February 2013. doi: 10.1007/s00455-0129441-x

Clave P, Arreola V, Romea M, Medina L, Palomera E, Serra-Prat M. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008;27:806-15. Popa Nita S, Murith M, Chisholm H, Engmann J. Matching the rheological

- 52 -

14.

Rofes L, Arreola V, Clave P. The volumeviscosity swallow test for clinical screening of Dysphagia and aspiration. Nestle Nutr Inst Workshop Ser 2012;72:33-42.

15.

Rosenbek J, Robbins J, Roecker E, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia 1996;11:93-8.

16.

The National Dysphagia Diet Task Force. National Dysphagia Diet: Standardization for Optimal Care. Chicago: American Dietetic Association, 2002.

17.

Prentice R. Correlated binary regression with covariates specific to each binary observation. Biometrics 1988;44:1033-48.

18.

Ickenstein GW, Riecker A, Höhlig C, Müller R, Becker U, Reichmann H, Prosiegel M. Pneumonia and in-hospital mortality in the context of neurogenic oropharyngeal dysphagia (NOD) in stroke and a new NOD step-wise concept. J Neurol 2010;257:14929.

19.

Hinchey JA, Shephard T, Furie K, Smith D, Wang D, Tonn S. Formal dysphagia screening protocols prevent pneumonia. Stroke 2005;36:1972-6.

20.

Almirall J, Rofes L, Serra-Prat M, Icart R, Palomera E, Arreola V, Clavé P. Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly. Eur Respir J 2013;41:923-8.

21.

Cohen JT, Manor Y. Swallowing disturbance questionnaire for detecting dysphagia. Laryngoscope 2011;121:1383-7.

22.

Pikus L, Levine MS, Yang YX, Rubesin SE, Katzka DA, Laufer I, Gefter WB. Videofluoroscopic Studies of Swallowing Dysfunction and the Relative Risk of Pneumonia. AJR Am J Roentgenol 2003; 180:1613-6.

23.

Daniels SK, McAdam CP, Brailey K, Foundas A. Clinical Assessment of Swallowing and Prediction of Dysphagia

Screening for oropharyngeal dysphagia Severity. Am 1997;6:17-24. 24.

25.

J

Speech

Lang

Pathol 30.

Mari F, Matei M, Ceravolo MG, Pisani A, Montesi A, Provinciali L. Predictive value of clinical indices in detecting aspiration in patients with neurological disorders. J Neurol Neurosurg Psychiatry 1997;63:456-60.

McCullough GH, Wertz RT, Rosenbek JC. Sensitivity and specificity of clinical/bedside examination signs for detecting aspiration in adults subsequent to stroke. J Commun Disord 2001;34:55-72.

31.

Smithard DG, O'Neill PA, Park C, England R, Renwick DS, Wyatt R, Morris J, Martin DF. Can bedside assessment reliably exclude aspiration following acute stroke? Age Ageing 1998;27:99-106.

Trapl M, Enderle P, Nowotny M, Teuschl Y, Matz K, Dachenhausen A, Brainin M. Dysphagia bedside screening for acutestroke patients: the Gugging Swallowing Screen. Stroke 2007;38:2948-52.

32.

Smith HA, Lee SH, O'Neill PA, Connolly MJ.. The combination of bedside swallowing assessment and oxygen saturation monitoring of swallowing in acute stroke: a safe and humane screening tool. Age Ageing 2000;29:495-9.

26.

DePippo KL, Holas MA, Reding MJ. Validation of the 3-oz water swallow test for aspiration following stroke. Arch Neurol 1992;49:1259-61.

27.

Lim SH, Lieu PK, Phua SY, Seshadri R, Venketasubramanian N, Lee SH, Choo PW. Accuracy of bedside clinical methods compared with fiberoptic endoscopic examination of swallowing (FEES) in determining the risk of aspiration in acute stroke patients. Dysphagia 2001;16:1-6.

33.

Hind JA, Gensler G, Brandt DK, Gardner PJ, Blumenthal L, Gramigna GD, Kosek S, Lundy D et al. Comparison of trained clinician ratings with expert ratings of aspiration on videofluoroscopic images from a randomized clinical trial. Dysphagia. 2009;24:211-7.

28.

Chong MS, Lieu PK, Sitoh YY, Meng YY, Leow LP. Bedside clinical methods useful as screening test for aspiration in elderly patients with recent and previous strokes. Ann Acad Med Singapore 2003;32:790-4. Logemann JA, Veis S, Colangelo L. A screening procedure for oropharyngeal dysphagia. Dysphagia 1999;14:44-51.

34.

Kelly AM, Drinnan MJ, Leslie P. Assessing penetration and aspiration: how do videofluoroscopy and fiberoptic endoscopic evaluation of swallowing compare? Laryngoscope. 2007;117:1723-7.

29.

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CAPÍTULO 2

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Swallow response in the frail elderly

Capítulo 2 PATHOPHYSIOLOGY OF OROPHARYNGEAL DYSPHAGIA IN THE FRAIL ELDERLY Laia Rofes, Viridiana Arreola, Maise Romea, Elisabeth Palomera, Jordi Almirall, Mateu Cabré, Mateu Serra-Prat, Pere Clavé. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010; 22(8): 851-8, e230.

Abstract Background: Oropharyngeal dysphagia is a major complaint among the elderly. Our aim is to assess the pathophysiology of oropharyngeal dysphagia in frail elderly patients. Methods: 45 frail elderly patients (FEP, 81.5±1.1 years) with oropharyngeal dysphagia and 12 healthy volunteers (HV, 40±2.4 years) were studied using videofluoroscopy. Each subject’s clinical records, signs of safety and efficacy of swallow, timing of swallow response, hyoid motion and tongue bolus propulsion forces were assessed. Results: HV presented a safe and efficacious swallow, faster laryngeal closure (0.157±0.013 seconds) and upper oesophageal sphincter opening (0.200±0.011 seconds), maximal vertical hyoid motion (0.310±0.048 seconds), and stronger tongue propulsion forces (22.16±2.54 mN) than FEP. In contrast, 63.63% of FEP presented oropharyngeal residue, 57.10%, laryngeal penetration and 17.14%, tracheobronchial aspiration. FEP with impaired swallow safety showed delayed laryngeal vestibule closure (0.476±0.047 seconds), similar bolus propulsion forces, poor functional capacity and higher 1-year mortality rates (51.7% vs 13.3%, p=0.021) than FEP with safe swallow. FEP patients with oropharyngeal residue showed impaired tongue propulsion (9.00±0.10 mN), delayed maximal vertical hyoid motion (0.612±0.071 seconds) and higher (56.0% vs 15.8%, p=0.012) 1-year mortality rates than those with efficient swallow. Conclusion: Frail elderly patients with oropharyngeal dysphagia presented poor outcome and high mortality rates. Impaired safety of deglutition and aspirations are mainly caused by delayed laryngeal vestibule closure. Impaired efficacy and residue are mainly related to weak tongue bolus propulsion forces and slow hyoid motion. Treatment of dysphagia in frail elderly patients should be targeted to improve these critical events.

Introduction Oropharyngeal dysphagia is a major complaint among the elderly. Functional oropharyngeal dysphagia affects more than 30% of patients who had a stroke; 52%-82% of those with Parkinson’s disease; it affects up to 84% of patients with Alzheimer’s disease, and more than 50% of elderly institutionalized patients (1;2). Aging is one of the principal demographic characteristics of developed countries. In the last decade, the population over 65 years of age has increased by 28 % whereas the rest of the population has only grown 0.8% (3). Up to 13.7% independent-living elderly people presented oropharyngeal dysphagia (4), and

16,500,000 US senior citizens will require care for dysphagia by the year 2010 (5). Among the elderly, the frail phenotype is an emerging clinical and research paradigm referring to aged individuals unusually susceptible to disease. Although the definition of frailty is still a matter of discussion and its relationships with aging, disability, and chronic disease have not been settled, it is well recognized that frailty correlates with vulnerability, general susceptibility to disease and poor outcome, including death (6). Oropharyngeal dysphagia may cause two groups of clinically relevant complications in older people: a) a decrease in the efficacy of deglutition present in up

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Capítulo 2___________________________________________________________________ to 25%-75% patients can lead to malnutrition and/or dehydration and b) a decrease in deglutition safety resulting in choking and tracheobronchial aspiration may result in pneumonia in 50% of cases (3;7). A recent 10-year review found a 93.5% increase in the number of hospitalized elderly patients with a diagnosis of aspiration pneumonia while other types of pneumonia in the elderly decreased (8). We recently found oropharyngeal dysphagia and aspiration is a highly prevalent (55%) clinical finding in elderly patients with pneumonia and is an indicator of pneumonia severity as patients with dysphagia showed lower functional status, higher prevalence of malnutrition, comorbidities, poor prognosis, and higher mortality rates (7). In elderly nursing home residents with oropharyngeal dysphagia, aspiration pneumonia occurs in 50% during the first year with a mortality rate above 45% (9). The pathophysiology of oropharyngeal dysphagia and the alterations of the biomechanics of swallow response and bolus kinematics in the frail elderly are not well understood. Videofluoroscopy (VFS) is the gold standard to study the oral and pharyngeal mechanisms of dysphagia (9). We previously found that slow closure of the laryngeal vestibule and slow opening of the upper oesophageal sphincter are the most characteristic aspiration-related events in neurological patients with oropharygeal dysphagia (10;11). Aspiration may also result from insufficient hyoid and laryngeal elevation, which would fail to protect the airway (11). We found efficacy of deglutition and oropharyngeal residue in neurological patients correlates well with impaired tongue bolus propulsion (10) and pharyngeal residue may lead to post-swallow aspiration (12).

examination. Frail elderly patients (n=45): patients over 70 years of age consecutively admitted to the Acute Geriatric Unit with respiratory (38.9%), neurological (13.9%), infectious (13.9%), cardiac (11.1%) or metabolic (11.1%) diseases; 48.8% of them coming from a nursing home. All patients had presented clinical complaints of oropharyngeal dysphagia during a routine clinical test we use for screening for oropharyngeal dysphagia and aspiration (13). A geriatric assessment on the day of admission included: a) demographic data, b) comorbidities with the Charlson Index (14) and presence of geriatric syndromes, c) functional capacity pre-admission (two weeks prior) and on admission, using the Barthel Index (15), d) nutritional status using the Mini Nutritional Assessment (MNA) (16) and e) a clinical test for oropharyngeal dysphagia and aspiration performed by an experienced speech-swallow therapist (7;13). Elderly patients were considered as “frail” if they fulfilled three or more of the following accepted criteria: 1) Unintentional weight loss of >5% of weight, 2) exhaustion (lower energy than usual, or feeling unusually tired or weak in the last month), 3) weakness (low strength with the hand dynamometer <7 kg in women and <14 kg in men), 4) walking slowness (≥7 seconds for 4.5 m), and 5) poor outdoor physical activity (17). After discharge a clinical follow up was performed 30 days after admission and a check up by telephone or visit a year after admission. Protocol studies were approved by the Institutional Review Board of the Hospital de Mataró (Mataró, Spain).

The aim of the present study is to assess the pathophysiology of oropharyngeal dysphagia in frail elderly patients in order to develop more specific therapeutic strategies to avoid nutritional and respiratory complications in this high vulnerable group of older patients.

Subjects were submitted to: a) a symptom inventory to assess the clinical severity of oropharyngeal dysphagia (18) and b) a videofluoroscopic study to assess the signs of safety and efficacy of deglutition and to measure the effect of bolus volume and viscosity, and the physiology of the swallow response (10;13) (Figure 1). VFS studies assessed the effect of increased volumes from 3, to 5, 10, 15 and 20 mL of liquid (20.40±0.23 mPa s), nectar (274.42±13.14 mPa s), and pudding viscosity (3931.23±166.15 mPa s) series according to our previous studies (10;13). Liquid viscosity was obtained by mixing 1:1 mineral water and the X-ray

Materials and Methods Sample Healthy volunteers (n=12), showed all parameters in the reference ranges during a general medical

Experimental Design

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Swallow response in the frail elderly contrast Gastrografin (Berlimed SA, Madrid, Spain), nectar viscosity by adding 3.5 g of thickener Resource ThickenUp (Nestlé Nutrition, Barcelona, Spain) to liquid solution and pudding viscosity by adding 8 g of the thickener. Bolus density for liquid -1 -1 was 1.19±0.007 g mL , nectar, 1.23±0.007 g mL , -1 and pudding, 1.27±0.001 g mL . Boluses were carefully offered to patients with a syringe (13).

Videofluoroscopic signs Patients were imaged while seated in a lateral projection which included the oral cavity, pharynx, larynx, and cervical esophagus (11;12) (Figure 1). VFS recordings were obtained by using a Super XT-20 Toshiba Intensifier (Toshiba Medical Systems Europe, Zoetermeer, Netherlands) and -1 images were recorded at 25 frames s (Panasonic AG DVX-100B, Matsushita Electric Industrial Co, Ltd, Osaka, Japan). Swallows were analyzed by equipment (Swallowing Observer, Image & Physiology SL, Barcelona, Spain) developed to capture and digitize the swallowing sequences to assess the VFS signs and measure the oropharyngeal swallow response (10;13). Oral and pharyngeal VFS signs of safety and efficacy of deglutition were identified accordingly to accepted definitions (12;14). Penetration was defined as the entrance of swallowed material into the laryngeal vestibule and aspiration as the passage of this material below the vocal cords (11). The severity of aspirations and penetrations was further characterized according to Rosenbek’s penetrationaspiration scale and according to whether they were followed by cough (silent aspirations) or not (11;19). Mechanisms of aspiration were classified as predeglutitive (before activation of pharyngeal phase), intra-deglutitive or post-deglutitive (11;15).

Oropharyngeal swallow response Measurements of oropharyngeal swallow response were obtained during 5 mL nectar swallows because all patients swallowed this bolus: a) Oropharyngeal reconfiguration, timing of the opening (O) or closing (C) events at the glossopalatal junction (GPJ), velopharyngeal junction (VPJ), laryngeal vestibule (LV), and upper esophageal sphincter (UES) were measured, GPJ

Figure 1 Oropharyngeal swallow response: A) Timing of opening and closing events at glossopalatal junction (GPJ), velopharyngeal junction (VPJ), laryngeal vestibule (LV) and upper esophageal sphincter (UES) were measured and all temporal measurements were referenced to glossopalatal junction opening (GPJO) as time 0. B) To assess extent and timing of hyoid movement, an X-Y coordinate system was used. The anterior-inferior corner of C3 was used as the origin, and the vertical axis was defined by a line connecting the anterior inferior corners of C3 and C5. C) Bolus kinematics. Bolus velocity (mean and maximal) and kinetic energy prior to enter the UESO were determined.

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Capítulo 2___________________________________________________________________ opening being given the time value 0 (11;16); b) hyoid motion (vertical and anterior movement) was determined in a X-Y coordinate system (11); c) anteroposterior diameter of UES opening (mm) (20;21); and d) bolus propulsion force of the tongue was measured by means of Newton’s second law of motion and expressed in mN; mean and maximal -1 velocity (m s ) and kinetic energy (mJ) acquired by the bolus prior to entering the UES (10;13) (Figure 1).

Data analysis and statistical methods Categorical variables were described as percentages. Patients with dysphagia were classified into those with safe deglutition and those with impaired safety (penetration or aspiration) and those with impaired efficacy according to whether they presented oropharyngeal residue (10). Quantitative parameters were described by mean±SEM and comparisons were assessed by the non-parametric Mann-Whitney U test. The effect of increasing bolus volume on safety and efficacy of deglutition was assessed by the non-parametric Cochran Q procedure, testing the null hypothesis that multiple-related prevalence are the same. The effect of increasing bolus viscosity was assessed by the non-parametric McNemar procedure testing the null hypothesis for related samples that multiple responses come from the same population. Hyoid profiles were compared by two-way ANOVA analysis and correlation analysis was assessed by the Spearman correlation coefficient. Statistical significance was accepted if p values were less than 0.05. Statistical analysis was performed by GraphPad Prism 4 (San Diego, CA, USA).

Results Demographics and clinical inventory scores Mean age of healthy volunteers was 40.2±2.5 years (6 men and 6 women) and that of frail elderly patients was 81.5±1.2 years (26 men and 19 women). The Charlson comorbidity index score of FEP was 2.2±0.2, chronic pneumopathy (45.9%), diabetes mellitus (29.7%), ischemic cardiopathy (24.3%), hearth failure (24.3%), cerebrovascular disease (21.6%) and dementia (16.2%) being highly

prevalent conditions among these frail patients. Mean body mass index of FEP was 25.8±0.9 Kg m 2 , and according to the MNA, 16% of FEP presented malnutrition and 48% were at risk of malnutrition. Patients with signs of penetration or aspiration during VFS studies showed poor functional capacity [Barthel Index pre-admission, 62.1±7.7 vs 92.3±3.3 in FEP with safe swallow (p=0.025), and on admission, 31.9±6.3 vs 68.6±6.9 in FEP with safe swallow, (p=0.002)] and increased mortality. Oneyear mortality was 51.7% among frail elderly patients with impaired safety signs on VFS study and 56.0% in those with impaired efficacy, whereas frail elderly patients with safe (13.3%, p=0.021) or efficient swallow (15.8%, p=0.012) had significantly lower mortality rates. Clinical severity of patients’ dysphagia score was significantly higher in FEP with impaired safety (548.9±68.7 points vs 155.8±52.3 in frail patients with safe swallow, p=0.001). Clinical severity scores were also higher for FEP with impaired efficacy and pharyngeal residue (503.2±76.7 points) although these differences did not reach statistical significance when compared with frail patients with efficient swallow (311.2±73.2 points, p=0.098).

Videofluoroscopic signs oropharyngeal dysphagia

of

Healthy volunteers: All volunteers presented a safe and efficacious swallow. Frail elderly patients: The effect of bolus volume and viscosity on the prevalence of VFS signs of impaired safety or efficacy of swallow is summarized in Figure 2. The prevalence of FEP with oral residue significantly increased by increasing bolus volume. Pudding viscosity also significantly increased oral residue. Pharyngeal residue was also a common VFS sign as impaired vallecular clearance was observed in up to 42.8% of patients during liquid series, 50% of patients during nectar series and increased to 63.3% of patients at pudding viscosity. Similarly, residue in the pyriform sinus was observed in 19.3% of patients during liquid series, 20% of patients during nectar series and increased to up to 38.5% of patients at pudding viscosity. Pharyngeal residue also significantly increased with bolus volume and pudding viscosity (Figure 2). Penetration into the laryngeal vestibule during the

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Swallow response in the frail elderly pharyngeal phase was the most prevalent cause of unsafe deglutition and was observed in up to 57.1% of FEP when swallowing liquid boluses and up to 52.8% of patients during nectar series. Increasing bolus viscosity to pudding significantly reduced prevalence of patients with laryngeal penetration to 20.5% (p<0.001). According to Rosenbek’s scale, 40% patients with impaired safety showed severe penetrations (levels 3-5). Aspiration into the airway during swallow response was observed in 17.1% of patients during liquid series and 9.1% at nectar

viscosity, and reduced to 6.8% with pudding viscosity. Also, 32.5% of patients with impaired safety had silent (level 8) aspirations. Only 4.5% of patients presented aspirations caused by postdeglutitive pharyngeal residue. Up to 53.3% of elderly patients could complete 3-20 mL pudding series safely; a proportion that was reduced to 33.3% during nectar (p=0.004) series and only 17.8% patients could complete the liquid series safely (p<0.001).

Figure 2 Prevalence of videofluoroscopic signs of safety and efficacy of oral preparatory, oral and pharyngeal phase of swallowing for each bolus volume and viscosity in Frail Elderly Patients with oropharyngeal dysphagia. Safety of laryngeal vestibule and vocal cord closure was expressed as the percentage of patients that could swallow without signs of contrast entering the laryngeal vestibule or traversing the vocal folds for each bolus volume and viscosity. * p<0.05, ** p<0.01, *** p<0.001 effect of increasing bolus volume; # p<0.05, ## p<0.01, ### p<0.001 vs liquid viscosity; † p<0.05, †† p<0.01, ††† p<0.001 vs nectar viscosity.

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Capítulo 2___________________________________________________________________

Oropharyngeal physiology Healthy volunteers: a) Duration of swallow response (GPJO-LVO) for 5 mL nectar boluses was 0.753±0.023 seconds. Oropharyngeal reconfiguration from a respiratory to a digestive pathway was very fast as time to close the airway entrance (GPJO-LVC) and time to open the UES (GPJO-UESO) was <0.200 seconds (Figure 3). b) Maximal extent of vertical hyoid movement was achieved at 0.310±0.048 seconds and maximal anterior hyoid motion occurred at 0.463±0.056 (Figure 4). c) UES opening during 5 mL bolus transit was 5.99±0.34 mm. d) Tongue bolus propulsion strength was 22.16±2.54 mN leading to high bolus velocity and kinetic energy (Figure 5). Frail elderly patients: a) Overall duration of swallow response was 0.985±0.037 seconds, significantly longer than in HV (p<0.001). The reconfiguration phase to a digestive pathway was also severely delayed in comparison to HV as time to close LV in FEP was 0.392±0.040 seconds (p<0.001), and time to UES opening was 0.384±0.032 seconds (p<0.001 vs HV). Time to LVC in frail elderly patients with penetration or

aspiration was significantly longer than that of elderly patients with safe swallow (Figure 3). Time to LVC and UESO was also significantly delayed in FEP with impaired efficacy when compared with patients without residue (Figure 3). b) The profile of vertical hyoid motion of FEP differed from healthy volunteers (p=0.001, Figure 4A) as maximal vertical hyoid motion was significantly delayed (0.480±0.055 seconds, p=0.022) in FEP. Among FEP, patients with impaired safety reached the maximal vertical extension later than patients with safe swallow, although these differences did not reach statistical significance in our study (Figure 4A); and time to maximal hyoid vertical movement was significantly prolonged in FEP with impaired efficacy, when compared with patients without residue (Figure 4A). In contrast, the profile of anterior hyoid motion of FEP was similar to that observed in HV (Figure 4B) and FEP achieved the maximal anterior extension in similar time (0.557±0.040 seconds, ns). Anterior hyoid movement was also similar among FEP with impaired safety or efficacy of swallow (Figure 4B).

Figure 3 Timing of main events of the oropharyngeal swallow response during 5 mL-nectar swallows in healthy volunteers (HV) and frail elderly patients (FEP) with dysphagia. Patients were stratified according the safety and efficacy of swallow. a) LVC: Laryngeal vestibule closure; b) UESO: Upper esophageal sphincter opening; c) LVO: Laryngeal vestibule opening; Safety + = safe swallow; Safety - = penetration or aspiration; Efficacy + = no oropharyngeal residue; Efficacy -: oropharyngeal residue. Open and full circles show aspiration and penetration times respectively. In HV and patients with safe swallow LVC preceded UES opening but this response was severely impaired in elderly patients with aspirations or penetrations, in whom LVC was delayed until after UESO. * p<0.05, ** p<0.01, *** p<0.001, # p<0.05 vs HV, ## p<0.01 vs HV, ### p<0.001 vs HV, ns: non significant.

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Swallow response in the frail elderly c) The extent of the upper esophageal sphincter opening in FEP was 5.40±0.22 mm, also similar to that of HV (p=0.286). d) Frail elderly patients presented weak tongue propulsion strength (8.99±1.09 mN, p<0.001 vs HV), leading to slow bolus velocity (0.409±0.027 m/s, p<0.001) and weak kinetic energy (0.577±0.072 mJ, p<0.001). FEP with safe swallow presented similar bolus

propulsion strength and similar mean and maximum bolus velocity and kinetic energy than elderly patients with penetration or aspirations (Figure 5). In contrast, patients with oropharyngeal residue presented weaker bolus propulsion forces and slower bolus velocity than elderly patients without oropharyngeal residue (Figure 5).

Figure 4 Vertical and anterior hyoid movement: a) Profiles of vertical (A) and anterior (B) hyoid movement in healthy volunteers (HV) and frail elderly patients (FEP) with dysphagia compared by two-way ANOVA analysis. b) Time of maximal vertical (A) and anterior (B) extent of hyoid in HV and FEP with dysphagia stratified according the safety and efficacy of swallow. * p<0.05, # p<0.05 vs HV, ## p<0.01 vs HV, ns: non significant.

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Capítulo 2___________________________________________________________________

Figure 5 Bolus strength and maximal and mean bolus velocity in healthy volunteers and elderly patients classified according to safety and efficacy of swallowing. HV: healthy volunteers; FEP: Frail elderly patients; Safety + = safe swallow; Safety - = penetration or aspiration; Efficacy + = no oropharyngeal residue; Efficacy -: oropharyngeal residue. * p<0.05, ** p<0.01, *** p<0.001, # p<0.05 vs HV, ## p<0.01 vs HV, ### p<0.001 vs HV, ns: non significant.

Discussion Our study shows that frail elderly patients admitted to a General Hospital for an acute disease showing clinical complaints of oropharyngeal dysphagia present severe videofluoroscopic signs of impaired safety and efficacy of swallow and are at high risk of respiratory complications and/or malnutrition and show poor survival. Oropharygeal dysphagia is associated to delayed and prolonged swallow response, weak tongue thrust and impaired hyoid motion. Aspirations and penetrations into the airways are specifically related to delayed laryngeal vestibule closure. Impaired efficacy is mainly characterized by oropharyngeal residue caused by weak tongue bolus propulsion forces and slow vertical hyoid motion. We found enhancing bolus viscosity greatly increased safety of oral and pharyngeal phases of swallowing in FEP; in contrast, increasing bolus volume severely impaired efficacy of deglutition in these patients. These results agree with our previous studies (10;13) and we believe oropharyngeal dysphagia should be recognized as a major geriatric syndrome and treatment should be targeted to improve these critical physiological events. Oropharyngeal dysphagia is a severe clinical symptom in elderly patients. We used a validated index based on mechanical dysfunction (18) and found that symptomatic severity of dysphagia in

FEP was similar to dysphagia associated with neurodegenerative diseases and more severe than dysphagia caused by a stroke (10). In contrast, oropharyngeal dysphagia is underestimated as a cause of symptoms and nutritional and respiratory complications in the elderly. Frailty is a biologic syndrome of decreased resistance to stressors, resulting from cumulative declines across multiple physiologic systems, and causing vulnerability to adverse outcomes including institutionalization, hospitalization, and death (6). Patients included in the present study fulfil the criteria of a validated and standardized phenotype of frailty in older adults with predictive validity for these adverse outcomes (17). Once oropharyngeal dysphagia was diagnosed in these frail elderly patients, our goal was to evaluate: a) swallowing efficacy, to ensure patients’ ability to ingest all the calories and water he or she needs, and b) swallowing safety, to avoid respiratory complications. By VFS, we found serious swallowing and cough reflex disorders in this group of FEP as more than half presented penetrations of ingested material into the laryngeal vestibule or aspirations beyond the vocal folds during the swallow response, many of them being silent due to simultaneous impairment of cough reflex (22). In addition, VFS signs of inefficient swallow showing impaired bolus control or weak tongue propulsion and leading to oropharyngeal residue were observed in up to two thirds of our FEP. Again, the

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Swallow response in the frail elderly prevalence and severity of VFS signs of impaired safety or efficacy of swallow exceeded those we found in patients with oropharyngeal dysphagia secondary to stroke and neurodegenerative diseases (10). Two thirds of our patients were at risk of malnutrition and the 1-year survival of our patients with impaired safety or efficacy of swallow was very poor. Aspiration pneumonia and malnutrition are two well-recognized complications of oropharyngeal dysphagia in the elderly (23). In a previous study, we found a 55% prevalence of clinical signs of aspiration in elderly patients with pneumonia, dysphagia being a marker of disease severity and poor prognosis and an independent factor strongly associated with 1-year mortality (7). However, dysphagia with oropharyngeal aspiration is rarely considered a risk factor in elderly patients with community-acquired pneumonia (14;15) or in elderly patients with malnutrition (16). The swallow response includes the arrangement of oropharyngeal structures from a respiratory to a digestive pathway, the transfer of the bolus from the mouth to the oesophagus, and the recuperation of the respiratory configuration (16). Transference of the bolus is mainly caused by the squeezing action of the tongue against the palate providing driving forces to propel swallowed material (24), and the pharyngeal contraction by the pharyngeal constrictor muscles facilitates pharyngeal clearance (25). We found the swallow response was severely impaired in FEP. First, overall duration of swallow response was significantly prolonged. Impaired safety is mainly associated with the delayed LVC. LVC occurs by anterior tilting of the arytenoid cartilages against the base of the epiglottis and by the descent of the epiglottis as a result of a hyolaryngeal elevation (11). Time to LVC is the time interval during which the potential aspiration occurs and is the key abnormality of oropharyngeal swallow response leading to unsafe deglutition in our elderly patients, in agreement with our previous studies (10;13) and an early study by Kahrilas that found that interval from GPJO-LVC leads to unsafe deglutition in neurological patients (9). Other studies have also shown that the strongest predictor of aspiration was the delay to hyoid elevation, as delayed hyoid movement contributes to delayed laryngeal closure (10). Vertical hyoid movement is mainly the result of suprahyoid and thyrohyoid

muscle contraction and we found that FEP have a poor and delayed vertical hyoid movement; in contrast the anterior hyoid motion was similar to that of HV. UES opening is caused by interruption of vagally-mediated contraction of cricopharyngeus muscle, anterior hyoid movement (11), and intrabolus pressure caused by tongue thrust (25;26). Our study shows that delayed UES opening is associated with residue in FEP. A recent study has also shown failed UES opening causes residue and postswallow aspiration in elderly patients with neurogenic dysphagia (21). However, in the present study, most aspirations occured during swallow response and are mainly associated with delayed LVC, suggesting that postswallow residue is not a main cause of impaired safety of swallow in FEP. Finally, low bolus propulsion forces leading to slower bolus velocity caused oropharyngeal residue in FEP. In contrast, aspirations and safety of deglutition were not related to tongue strength, showing specific and independent mechanisms for impaired safety and efficacy of swallow in FEP. Impaired swallow response in the frail elderly might be caused by neurogenic and myogenic factors. Studies in healthy people over 80 years of age found normal aging delays and prolonged swallow response and increased oropharyngeal residue (2729). Delayed swallow response has been attributed to impaired function of peripheral afferents to the swallowing centre and slow synaptic conduction in the central nervous system caused by high prevalence of neurological and neurodegenerative diseases in the frail elderly as well as the neurodegenerative process related to ageing (30). Drugs with detrimental effects on consciousness or swallow response can also contribute to delayed swallow response (7). On the other hand, weak muscular tongue strength caused by sarcopenia is the major contributor to impaired bolus propulsion (5). All these pathophysiological factors causing dysphagia in the frail elderly can be potentially treated: a) stimulation of TRPV1 receptors located in afferent sensory fibres from the larynx (superior laryngeal nerve) or the pharynx (pharyngeal branch of the glossopharyngeal nerve) by acid, thermal stimulation or specific TRPV1 agonists might speed the neural swallow responses (31-35); b) rehabilitation by lingual resistance exercises is an effective treatment for patients with lingual

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Capítulo 2___________________________________________________________________ weakness and dysphagia due to frailty (36); and c) the classical suprahyoid exercise program (Shaker manoeuvre) improves hyoid motion and UES opening (21) and electrical stimulation of suprahyoid muscles also showed hyoid and laryngeal elevation can be improved (37). Finally, increasing bolus viscosity in our study improved VFS signs of safety and efficacy of swallow in elderly patients (10). Taken together, all these observations suggest that oropharyngeal dysphagia in the frail elderly can be treated by using these individual or combined therapeutic strategies. There is a big discrepancy between the high prevalence, morbidity, mortality and costs caused by nutritional and respiratory complications of oropharyngeal dysphagia in frail elderly and the low level of resources dedicated to assess and treat dysphagia in these patients. In the present study we have explored the specific pathophysiology of dysphagia in FEP patients suggesting potential therapeutic options. We believe oropharyngeal dysphagia fulfils most criteria to be recognized as a major geriatric syndrome as its prevalence is very high in geriatric people, it results in multiple diseases, risk factors and precipitating diseases in frail older patients and represents a specific target for therapeutic interventions (4;38).

2.

3.

J

Rehabil

Res

Dev

6.

Bergman H, Ferrucci L, Guralnik J et al. Frailty: an emerging research and clinical paradigm--issues and controversies. J Gerontol A Biol Sci Med Sci 2007;62:731-7.

7.

Cabre M, Serra-Prat M, Palomera E, Almirall J, Pallares R, Clave P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010; 39: 39-45.

8.

Baine WB, Yu W, Summe JP. Epidemiologic trends in the hospitalization of elderly Medicare patients for pneumonia, 1991-1998. Am J Public Health 2001;91:1121-3.

9.

Cook IJ, Kahrilas PJ. AGA technical review on management of oropharyngeal dysphagia. Gastroenterology 1999;116:455-78.

10.

Clave P, de Kraa M, Arreola V et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006;24:1385-94.

11.

Kahrilas PJ, Lin S, Rademaker AW, Logemann JA. Impaired deglutitive airway protection: a videofluoroscopic analysis of severity and mechanism. Gastroenterology 1997;113:1457-64.

12.

Logemann JA. Manual for the videofluorographic study of swallowing. 2nd ed. Austin: PRO-ED; 1993.

13.

Lin LC, Wu SC, Chen HS, Wang TG, Chen MY. Prevalence of impaired swallowing in institutionalized older people in Taiwan. J Am Geriatr Soc 2002;50:1118-23.

Clave P, Arreola V, Romea M, Medina L, Palomera E, Serra-Prat M. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008;27:806-15.

14.

Clave P, Verdaguer A, Arreola V. [Oralpharyngeal dysphagia in the elderly]. Med Clin (Barc) 2005;124:742-8.

Logemann JA. Dysphagia: evaluation and treatment. Folia Phoniatr Logop 1995;47:14064.

15.

Medda BK, Kern M, Ren J et al. Relative contribution of various airway protective mechanisms to prevention of aspiration during swallowing. Am J Physiol Gastrointest Liver Physiol 2003;284:G933-G939.

16.

Kahrilas PJ, Lin S, Chen J, Logemann JA. Oropharyngeal accommodation to swallow volume. Gastroenterology 1996;111:297-306.

References 1.

Experts Meeting. 2002;39:543-8.

Ekberg O, Hamdy S, Woisard V, WuttgeHannig A, Ortega P. Social and psychological burden of dysphagia: its impact on diagnosis and treatment. Dysphagia 2002;17:139-46.

4.

Turley R, Cohen S. Impact of voice and swallowing problems in the elderly. Otolaryngol Head Neck Surg 2009;140:33-6.

5.

Robbins J, Langmore S, Hind JA, Erlichman M. Dysphagia research in the 21st century and beyond: proceedings from Dysphagia

- 66 -

Swallow response in the frail elderly 17.

18.

19.

20.

Fried LP, Tangen CM, Walston J et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146M156.

29.

Yoshikawa M, Yoshida M, Nagasaki T et al. Aspects of swallowing in healthy dentate elderly persons older than 80 years. J Gerontol A Biol Sci Med Sci 2005;60:506-9.

30.

Nagaya M, Sumi Y. Reaction time in the submental muscles of normal older people. J Am Geriatr Soc 2002;50:975-6.

Rosenbek J, Robbins J, Roecker E. A penetration-aspiration scale. Dysphagia 1996;11:93-8.

31.

Kahrilas PJ, Logemann JA, Krugler C, Flanagan E. Volitional augmentation of upper esophageal sphincter opening during swallowing. Am J Physiol 1991;260:G450G456.

Ebihara T, Takahashi H, Ebihara S et al. Capsaicin troche for swallowing dysfunction in older people. J Am Geriatr Soc 2005;53:8248.

32.

Ebihara T, Sekizawa K, Nakazawa H, Sasaki H. Capsaicin and swallowing reflex. Lancet 1993;341:432.

33.

Watando A, Ebihara S, Ebihara T et al. Effect of temperature on swallowing reflex in elderly patients with aspiration pneumonia. J Am Geriatr Soc 2004;52:2143-4.

34.

Logemann JA, Pauloski BR, Colangelo L, Lazarus C, Fujiu M, Kahrilas PJ. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995;38:55663.

35.

Hamdy S, Jilani S, Price V, Parker C, Hall N, Power M. Modulation of human swallowing behaviour by thermal and chemical stimulation in health and after brain injury. Neurogastroenterol Motil 2003;15:69-77.

36.

Robbins J, Gangnon RE, Theis SM, Kays SA, Hewitt AL, Hind JA. The effects of lingual exercise on swallowing in older adults. J Am Geriatr Soc 2005;53:1483-9.

37.

Burnett TA, Mann EA, Stoklosa JB, Ludlow CL. Self-triggered functional electrical stimulation during swallowing. J Neurophysiol 2005;94:4011-8.

38.

Flacker JM. What is a geriatric syndrome anyway? J Am Geriatr Soc 2003;51:574-6.

Wallace KL, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of oral-pharyngeal dysphagia. Gastroenterology 2000;118:678-87.

21.

Shaker R, Easterling C, Kern M et al. Rehabilitation of swallowing by exercise in tube-fed patients with pharyngeal dysphagia secondary to abnormal UES opening. Gastroenterology 2002;122:1314-21.

22.

Marik PE, Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest 2003;124:328-36.

23.

Almirall J, Cabre M, Clave P. Aspiration pnemonia. Med Clin (Barc) 2007;129:424-32.

24.

Nicosia MA, Robbins JA. The fluid mechanics of bolus ejection from the oral cavity. J Biomech 2001;34:1537-44.

25.

Kahrilas PJ, Logemann JA, Lin S, Ergun GA. Pharyngeal clearance during swallowing: a combined manometric and videofluoroscopic study. Gastroenterology 1992;103:128-36.

26.

older men. J Speech Lang Hear Res 2000;43:1264-74.

Williams RB, Pal A, Brasseur JG, Cook IJ. Space-time pressure structure of pharyngoesophageal segment during swallowing. Am J Physiol Gastrointest Liver Physiol 2001;281:G1290-G1300.

27.

Robbins J, Hamilton JW, Lof GL, Kempster GB. Oropharyngeal swallowing in normal adults of different ages. Gastroenterology 1992;103:823-9.

28.

Logemann JA, Pauloski BR, Rademaker AW, Colangelo LA, Kahrilas PJ, Smith CH. Temporal and biomechanical characteristics of oropharyngeal swallow in younger and

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CAPÍTULO 3

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OD is a risk factor for CAP in the elderly

Capítulo 3 OROPHARYNGEAL DYSPHAGIA IS A RISK FACTOR FOR COMMUNITYACQUIRED PNEUMONIA IN THE ELDERLY Jordi Almirall*, Laia Rofes*, Mateu Serra-Prat, Roser Icart, Elisabet Palomera, Viridiana Arreola, Pere Clavé. Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly. Eur Respir J 2013; 41(4): 923-8. *Co-first authors.

Abstract Objective: To explore whether oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly and to assess the physiology of deglutition of patients with pneumonia. Methods: Case-control study: 36 elderly patients (>70 years) hospitalized with pneumonia were matched by age and sex with two independently-living controls. All subjects were given the volume-viscosity swallow test to identify signs of oropharyngeal dysphagia. Pathophysiological study: All cases and 10 healthy elderly were examined with videofluoroscopy. Results: Case-control study: Prevalence of oropharyngeal dysphagia was 91.7% in cases and 40.3% in controls (p<0.001). Adjusting for functionality and co-morbidities, dysphagia showed an independent effect on pneumonia (OR=11.9, 95% CI:3.03-46.9). Pathophysiological study: Among cases, 16.7% showed safe swallow, 30.6% high penetrations, 36.1% severe penetrations and 16.7% silent aspirations during videofluoroscopy, while in the healthy elderly these percentages were 80.0%, 20.0%, 0% and 0%, respectively (p<0.001). A delay in the laryngeal vestibule closure (0.414±0.029s vs 0.200±0.059s, p<0.01) was the main mechanism of impaired airway protection. Conclusions: In elderly subjects, oropharyngeal dysphagia is strongly associated with community-acquired pneumonia independently of functionality and co-morbidities. Elderly patients with pneumonia presented a severe impairment of swallow and airway protection mechanisms. We recommend universal screening of dysphagia in older persons with pneumonia.

Introduction Community-acquired pneumonia (CAP) is a common disease and a frequent cause of hospitalization and death among the elderly[1]. According to population-based studies, the annual incidence rate of CAP in adults varies between 2.6 and 13.4 per 1,000 inhabitants, somewhat higher in elderly people[2;3]. Studies found old age as a relevant risk factor for the acquisition of pneumonia[4]. Other associated factors that predispose to CAP in the elderly include: lifestyle and patient characteristics such as smoking, alcohol use, poor functional and nutritional status, weight loss and use of immunosuppressants; comorbidities such as heart diseases, renal diseases and chronic obstructive pulmonary disease; and

environmental exposure such as secondhand smoke, gases, fumes and chemicals[5-7]. We recently found oropharyngeal dysphagia was also a highly prevalent clinical finding in up to 23% of independently living older (>70 y) persons, 0.74% of them presenting signs of aspiration during swallow[8]. In these patients with oropharyngeal dysphagia, a decrease in the efficacy of deglutition was associated with development of malnutrition and a decrease in the safety was associated with high prevalence of respiratory infections during follow up[9]. Oropharyngeal dysphagia has been identified as a serious risk factor for developing aspiration pneumonia in frail older people[10]. The pathogenesis of aspiration pneumonia in immunocompetent adults has been attributed to pharyngeal colonization of respiratory pathogens

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Capítulo 3___________________________________________________________________ and subsequent inhalation of infectious particles[11]. Oropharyngeal dysphagia has also been proposed as an independent risk factor associated with CAP in the elderly[6;12;13] but this has not yet been proved. Moreover, the pathogenic mechanism that leads to oropharyngeal dysphagia in the frail elderly and in neurological patients has been identified in recent years[14;15]. In contrast, the pathophysiology of impaired swallow response of elderly people with pneumonia has not yet been studied. The present study has two main objectives: i) to provide further evidence of the association between oropharyngeal dysphagia and CAP in the elderly and ii) to assess the pathophysiology of oropharyngeal dysphagia in elderly subjects with CAP.

Materials and Methods Case-control study An observational case-control study was designed. The study protocol was approved by the Ethics Committee of Consorci Sanitari del Maresme (Mataró, Spain). Cases were defined as subjects ≥70 years with confirmed CAP that required hospitalization in the Hospital of Mataró from February 2008 to February 2010 and were consecutively included in the study as long as videofluoroscopic examination was available. We have described the criteria for the diagnosis of CAP previously[2]. Patients from nursing homes or those that had been discharged from hospital 7 or fewer days before the onset of symptoms were excluded. For each case, two matched (by sex and age) controls without CAP were randomly selected from the list of independently-living older subjects assigned to the Cirera-Molins Primary Care Centre in Mataró (Spain). All cases and controls were explored by the volume-viscosity swallow test (see the on-line supplementary material) to assess the clinical signs for oropharyngeal dysphagia and impaired efficacy and safety of swallow. Comorbidities and pre-admission functional capacity were also registered for all participants.

Pathophysiological study a) Clinical characteristics of pneumonia and concomitant medications were collected in all cases. Vaccination history, number of previous pneumonias, fever, days of clinical symptoms, lobes affected, severity of CAP[16], Intensive Care Unit admissions and hospital death were recorded. To determine the etiology of pneumonia, blood cultures (n=30) and urine antigen tests for S. pneumoniae (n=30) and L. pneumophila (n=33) were performed. Whenever possible, respiratory samples were also obtained: sputum (n=9), tracheal aspirate (n=1) and pleural fluid (n=2). A sublingual smear (n=29) was also obtained to assess the oral flora. b) 10 healthy elderly persons (≥70 years) and all patients with CAP were studied by videofluoroscopy during the admission. Details on the videofluorscopic procedures are provided in the online supplementary material. Digitization and analysis of videofluoroscopic images were made using the software Swallowing Observer (Image and Physiology SL, Barcelona, Spain). Laryngeal vestibule penetrations and tracheobronchial aspirations were classified according to a validated scale[17] and oropharyngeal residue was also identified. Timing of the oropharyngeal swallow response, hyoid bone movement and bolus velocity -1 (m s ) were also measured[14]. c) CAP patients were followed through the electronic clinical records of the hospital of Mataró for one year or contacted by telephone one year after discharge in order to register death or readmissions caused by lower respiratory tract infections. If telephone contact could not be made, patients’ family doctors were contacted.

Statistical analysis Categorical variables were described as percentages and compared by the Chi-square test or the Fisher exact test when appropriate. Quantitative variables were described as mean±SEM and compared by the Mann–Whitney U-test. As a measure of association between oropharyngeal dysphagia, impaired efficacy and safety of swallow and pneumonia, estimations of the relative risk through odds ratios (OR) and 95% confidence intervals (CI) were calculated. The effect of oropharyngeal dysphagia and impaired safety

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OD is a risk factor for CAP in the elderly and efficacy of swallow on the risk of the development of CAP was adjusted by comorbidities and pre-admission functional capacity in a multivariate model using logistic regression. Survival curves according to safety of swallow were compared using a Log rank test. Statistical significance was accepted if P values were less than 0.05. Statistical analysis was performed using SPSS 15.0 (SPSS Inc., Chicago, USA).

(81.22±0.77 years, 24 men) were finally included in the study and matched with 72 controls (81.21±0.53 years, 48 men). The univariate analysis showed that the prevalence of oropharyngeal dysphagia and clinical signs of impaired efficacy and safety of swallow were higher in cases than in controls (Table 1). Cases also presented lower functional capacity than controls according to the Barthel Index (67.1 vs 97.4, p<0.001) and higher prevalence of chronic bronchitis/chronic obstructive pulmonary disease (COPD) and chronic heart failure. A multivariate logistic regression analysis showed an independent effect of oropharyngeal dysphagia related to the development of CAP when adjusting for suboptimal Barthel Index scores (<100), chronic bronchitis/COPD and chronic heart failure (Table 2).

Results Case-control study 45 cases with CAP were screened during the study period and 9 cases were excluded because patients were discharged before the videofluoroscopic examination was available. 36 cases with CAP

Table 1. Univariate analysis of risk factors associated with pneumonia in the elderly. Data presented as number of cases (percentage). COPD indicates chronic obstructive pulmonary disease; OR, Odds Ratio; CI, confidence interval.

Cases (N=36)

Controls (N=72)

P value

OR

95% CI

25 (69.4%)

18 (25.0%)

<0.001

6.82

2.81-16.6

18 (50%)

20 (27.8%)

0.023

2.60

1.13-5.98

Chronic heart failure

16 (44.4%)

15 (21.1%)

0.012

2.99

1.25-7.13

Benzodiazepine use

10 (27.8%)

16 (22.2 %)

0.254

1.34

0.54-3.37

33 (91.7%)

29 (40.3%)

<0.001

16.3

4.57-58.2

22 (61.1%)

18 (25.0%)

<0.001

4.71

2.00-11.1

30 (83.3%)

24 (33.3%)

<0.001

10.0

3.66-27.3

Barthel Index (<100) COPD/Chronic bronchitis

Oropharyngeal dysphagia Safety impairment Efficacy impairment

Table 2. Multivariate logistic regression analysis of risk factors associated with pneumonia in the elderly. COPD indicates chronic obstructive pulmonary disease; OR, Odds Ratio; CI, confidence interval.

P value

OR

95% CI

Barthel Index (<100)

0.001

6.93

2.13 -22.5

COPD/Chronic bronchitis

0.032

3.80

1.12 -12.9

Chronic heart failure

0.184

2.19

0.69 -6.95

Oropharyngeal dysphagia

<0.001

11.9

3.03 -46.9

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Capítulo 3___________________________________________________________________

Pathophysiological study a) General characteristics and etiology of pneumonia. General features of patients with pneumonia are described in Table 3. Most of them were treated with corticosteroids (55.6%) and beta(2)-agonists (55.6%); 15 (41.7%) received proton-pump inhibitors; 13, diuretics (36.1%) and 12, ACE inhibitors (33.3%). Patients that received SNC-acting drugs were: 10, (27.8%) benzodiazepines; 6, (16.7%) antidepressants; 3, (8.3%) neuroleptics and 3, (8.3%) antiparkinsonians. The aetiological diagnosis of pneumonia was achieved in 20 patients (55.6%). Streptococcus pneumoniae was found in 17 (47.2%), of whom 9 (52.9%) presented impaired safety of swallow and 8 (47.1%) presented safe swallow. Pseudomonas aeruginosa (2.8%), Klebsiella penumoniae (2.8%) and a co-infection of Pseudomonas aeruginosa and Klebsiella penumoniae (2.8%) were also found as etiologic agents in patients with impaired safety of swallow. On the other hand, normal oral flora was found in 69.0% of oral smears. Candida albicans (8.3%), Pseudomonas aeruginosa (8.3%), Klebsiella penumoniae (2.8%) and Streptococcus agalactiae (2.8%) were the pathogens isolated from patients’ oral cavity. Table 3. Clinical characteristics of patients. Data presented as number of cases (percentage), except *mean (SD). RUL, right upper lobe; RLL, right lower lobe; ML, middle lobe; LUL, left upper lobe; LLL, left lower lobe; PSI, pneumonia severity index; ICU, intensive care unit.

N=36 Influenza vaccination Pneumococcal vaccination Number of previous pneumonias: 0 1 ≥2 Body temperature <37º Days of clinical symptoms* Lung location: RUL RLL ML LUL LLL Number of affected lobes ≥2 PSI: I II III IV V CRB-65* ICU admission Hospital death

20 (55.6%) 5 (13.9%) 25 (69.4%) 8 (22.2%) 3 (8.3%) 11 (30.6%) 3.9 (3.6) 14 (38.9%) 11 (30.6%) 3 (8.3%) 3 (8.3%) 11 (30.6%) 6 (16.7%) 0 0 8 (22.2%) 21 (58.3%) 7 (19.4%) 2.0 (0.9) 7 (19.4%) 3 (9.7%)

b) Videofluoroscopic study. Efficacious swallows without any residue during all series of the videofluoroscopic study were observed in 60% of healthy elderly persons (75.80±0.97 years, 70% men) and in 41.67% of elderly patients with CAP (p=0.066) (Figure 1). Safe swallows (score 1 on the penetration-aspiration scale) were observed in 80% of healthy elderly persons, and high penetrations into the laryngeal vestibule (score 2) in 20%. In contrast, 16.7% of elderly patients with CAP showed safe swallow (p<0.001), 30.6% presented high penetrations, 36.1% severe penetrations into the laryngeal vestibule (not ejected from the airways and/or contacting the vocal folds, scores 3-5) and 16.7% silent aspirations (score 8) (Figure 1). General prevalence of oropharyngeal dysphagia among CAP patients according to the videofluoroscopic study was 75.0%. In healthy elderly, total duration of swallow response (time from glossopalatal junction opening to laryngeal vestibule opening) for 5 mL nectar boluses was 0.888±0.042 s, the interval for oropharyngeal reconfiguration from a respiratory to a digestive pathway (time to laryngeal vestibule closure) was 0.240±0.039, and timing of upper esophageal sphincter opening was 0.276±0.039 s. Elderly patients with CAP showed similar duration of swallow response (1.00±0.042 s, p=0.241) and time to upper esophageal sphincter opening (0.333±0.025 s, p=0.178) as healthy elderly persons, but a significant delay in laryngeal vestibule closure (0.414±0.029 s, p=0.002). When comparing elderly patients with CAP according to the safety of swallow, patients with safe swallow (scores 1-2 on the penetration-aspiration scale) showed a significantly shorter laryngeal vestibule closure time than patients with impaired safety of swallow (scores 3-8) (Figure 2). In contrast, no differences were found in the timing of upper esophageal sphincter opening (0.287±0.024 s and 0.375±0.040 s respectively, p=0.144) or the total duration of swallow response (0.948±0.039 s and 1.05±0.071 s respectively, p=0.437). Regarding hyoid bone movement, healthy elderly persons achieved maximal vertical extension in 0.314±0.041 s and maximal anterior extension in 0.349±0.058 s. Elderly patients with CAP reached maximal vertical and anterior extension significantly later (0.437±0.039 s and 0.549±0.040 s, p<0.05). CAP patients with impaired safety of swallow also

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OD is a risk factor for CAP in the elderly achieved maximal vertical extension later than CAP patients with safe swallow (Figure 3). Maximal vertical and anterior hyoid displacement was similar among groups (data not shown). Finally, the maximal velocity acquired by the bolus at the upper esophageal sphincter was very similar between -1 healthy elderly (0.481±0.073 m s ) and elderly -1 patients with CAP (0.482±0.035 m s , p=0.946) and was not affected by impairment in the safety of swallow. c) 1-year follow up. CAP patients with impaired safety of swallow showed decreased survival rates compared to patients with safe swallow 1 year after admission (Figure 4). Up to 50.00% of CAP patients with safe swallow and 71.43% with impaired safety of swallow (p=0.201) were readmitted during the follow up with lower respiratory tract infections.

Figure 2. Laryngeal vestibule closure time. Patients with CAP were divided into patients with safe swallow (scores 1-2) and patients with impaired safety of swallow (scores 3-8). Each box plot graphs the median, 10th, 25th, 75th and 90th percentiles. *p<0.05, **p<0.01, ***p<0.001.

Figure 1. Prevalence of main videofluoroscopic signs of efficacy (A) and safety (B) of swallow. Prevalence is expressed as number of subjects with sign presence versus total number of subjects. ***p<0.001.

Discussion The most remarkable finding of our study was that oropharyngeal dysphagia is strongly associated with CAP and should be considered as an independent risk factor for CAP in the elderly. The clinical assessment of oropharyngeal dysphagia showed that prevalence of dysphagia and impaired efficacy and safety of swallow among elderly patients with CAP was very high compared to matched controls. These clinical results were confirmed by the gold standard for swallowing evaluation, videofluoroscopy. The videfluoroscopic

study showed that 52.8% of elderly patients with CAP presented severe penetrations or aspirations during swallow. We also observed a high prevalence of oropharyngeal residue in these patients. Oropharyngeal residue is also an important finding, as it can predispose to oral colonization and post-swallow aspirations[18]. Finally, the oropharyngeal swallow response was severely impaired in our elderly patients with CAP. A severe delay in the oropharyngeal reconfiguration from a respiratory phase to a digestive phase, caused by slow laryngeal vestibule closure and

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Capítulo 3___________________________________________________________________

Figure 3. Hyoid movement. Time of maximal hyoid vertical (A) and anterior (B) extension of healthy elderly and patients with CAP divided into patients with safe swallow (scores 1-2) and patients with impaired safety of swallow (scores 3-8). Each box plot graphs the median, 10th, 25th, 75th and 90th percentiles. *p<0.05, **p<0.01.

Figure 4. Survival curves. Accumulated survivals of patients with CAP at 1 year according to the impairment of swallow (safe swallow, scores 1-2 and impaired safety of swallow, scores 3-8).

vertical hyoid motion, was the key parameter associated with impaired safety of swallow. Diagnostic etiology of pneumonia was achieved in half the cases. All patients with CAP and safe swallow presented Streptococcus pneumoniae as the etiologic agent of pneumonia. Most patients with impaired safety of swallow also presented Streptococcus pneumoniae as the etiologic agent, followed by Gram-negative bacilli. Taken together, our data strongly suggests that aspiration among patients with CAP is much more common than was believed and is a relevant pathogenic mechanism for older patients with pneumococcal CAP as well as for those with Gram-negative pneumonia.

Some studies have discussed the importance of aspiration and swallowing impairment in developing CAP[6;12] in elderly patients but, as far as we know, the present study is the first that evaluates the specific role of dysphagia as a predisposing and prognostic factor for CAP in the elderly and that assesses the mechanisms of the impaired swallow response of elderly patients with CAP. Moreover, the assessment of dysphagia was made prospectively, both in cases and controls. The prospective evaluation of dysphagia is a relevant point because dysphagia is often underdiagnosed and several cases may be missed in clinical records. We used an accurate and validated clinical method for the clinical assessment of dysphagia, the volume-viscosity swallow test, and found that not only impaired safety of swallow is associated with CAP, but impaired efficacy of swallow is also a risk factor for CAP in the elderly. In healthy people, the effective clearance of most of pathogens from the oropharynx is due to effective salivary flow and efficient swallowing. Therefore, when the efficacy of swallow is impaired, a reduction in mechanical clearance occurs leading to oropharyngal residue, and potential pulmonary or oropharyngeal pathogens may colonize the oropharynx and be a potential source of pulmonary infections[19]. Teramoto et al[20] reported that the prevalence of aspiration pneumonia in patients with CAP aged 70 and older was 60.1% using a wide variety of clinical assessment methods. We found a prevalence of

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OD is a risk factor for CAP in the elderly oropharyngeal dysphagia among patients with CAP of 91.7% by means of the volume-viscosity swallow test and of 75.00% in the videofluoroscopic study, with 52.8% the patients having severe penetrations or aspirations during swallow. This is the first time, to the authors’ knowledge, that a gold standard, videofluoroscopy, has been used to assess the prevalence of aspiration during swallow in elderly patients admitted with CAP. Prevalence of silent aspirations in our study was 16.7%. A previous study, using a radioactive tracer, found that the occurrence of silent aspiration during sleep was 71% in CAP patients whereas only 10% of aged matched controls aspirated[21]. The aspiration of small amounts of oropharyngeal secretions during sleep is a common finding in older adults[22;23] and usually happen without consequences due to preserved cough reflex, ciliary transport and immune system and to the low virulence of normal pharyngeal flora. However silent aspiration of large amounts during swallowing is an abnormal and serious finding that, together with several factors common in the elderly such as progressive decrease in pulmonary function, decline in host defenses, impaired cough reflex and increased oropharyngeal colonization with respiratory pathogens[19], can lead to aspiration pneumonia. A key point of our study is that we elucidated the pathogenic mechanism of the aspiration process and impaired airway protection of patients with CAP through videofluoroscopy. Delayed airway protection caused by delayed laryngeal vestibule closure and vertical hyoid movement caused the aspirations and penetrations in elderly CAP patients. This impairment in swallow response is similar to that found in frail elderly patients[14] and patients with neurological diseases[15] and must be treated. Our results show that impaired safety of swallow is a prognostic factor of mortality in elderly patients with CAP. These results agree with that found by Riquelme et al[12] and with one of our previous studies in patients with pneumonia admitted to an acute geriatric unit[24]. Again, use of the videofluoroscopy to determine patients with a predisposition to aspiration improves the diagnosis of aspiration pneumonia and confirms the results found by these previous studies using clinical records or clinical methods of screening.

A limitation of our study is that swallowing ability was not re-evaluated after discharge to assess whether these patients had improved after the acute condition and also those who had deteriorated over time. Therefore our design cannot exclude CAP as the cause of the swallowing problem. Another limitation was the small sample size. It was large enough to determine dysphagia as a risk factor for CAP, to characterize the swallow response of CAP patients and to evaluate the impairment of swallow response as a prognostic factor. However, the small size limits the microbiological and clinical comparisons between CAP patients with and without oropharyngeal dysphagia. Further studies are needed in this area including the assessment of the oral health status and the use of molecular strategies to improve the assessment of the oral microbiota in these patients. On the other hand, although cases and controls were matched by age and sex, they could not be strictly comparable in terms of co-morbidities, functional capacity or frailty. However, the multivariate analysis adjusted for the mentioned factors showed an independent effect of oropharyngeal dysphagia. In summary, we have confirmed that oropharyngeal dysphagia is a major risk and prognostic factor for CAP in the elderly. We have established its high prevalence by means of a gold standard and determined that the pathogenic mechanism of impairment of swallow response in this cohort of patients with CAP was delayed airway protection. Therefore, we propose universal screening for oropharyngeal dysphagia in elderly patients admitted with CAP and the adoption of strategies to assess and treat oropharyngeal dysphagia when aspiration is suspected.

References

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1. Jackson ML, Neuzil KM, Thompson WW, Shay DK, Yu O, Hanson CA, Jackson LA. The burden of community-acquired pneumonia in seniors: results of a populationbased study. Clin Infect Dis 2004; 39:16421650. 2. Almirall J, Bolibar I, Vidal J, Sauca G, Coll P, Niklasson B, Bartolome M, Balanzo X. Epidemiology of community-acquired

Capítulo 3___________________________________________________________________ pneumonia in adults: a population-based study. Eur Respir J 2000; 15:757-763. 3. Jokinen C, Heiskanen L, Juvonen H, Kallinen S, Karkola K, Korppi M, Kurki S, Ronnberg PR, Seppa A, Soimakallio S, . Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol 1993; 137:977-988. 4. Loeb M, McGeer A, McArthur M, Walter S, Simor AE. Risk factors for pneumonia and other lower respiratory tract infections in elderly residents of long-term care facilities. Arch Intern Med 1999; 159:2058-2064. 5. Jackson ML, Nelson JC, Jackson LA. Risk factors for community-acquired pneumonia in immunocompetent seniors. J Am Geriatr Soc 2009; 57:882-888. 6. Loeb M, Neupane B, Walter SD, Hanning R, Carusone SC, Lewis D, Krueger P, Simor AE, Nicolle L, Marrie TJ. Environmental risk factors for community-acquired pneumonia hospitalization in older adults. J Am Geriatr Soc 2009; 57:1036-1040. 7. Koivula I, Sten M, Makela PH. Risk factors for pneumonia in the elderly. Am J Med 1994; 96:313-320. 8. Serra-Prat M, Hinojosa G, Lopez D, Juan M, Fabre E, Voss DS, Calvo M, Marta V, Ribo L, Palomera E, Arreola V, Clave P. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in independently living older persons. J Am Geriatr Soc 2011; 59:186-187. 9. Serra-Prat M, Palomera M, Gomez C, SarShalom D, Saiz A, Montoya JG, Navajas M, Palomera E, Clavé P. Oropharyngeal dysphagia as a risk factor for malnutrition and lower respiratory tract infection in independently-living older persons: a population-based prospective study. Age Ageing 2012. 10. van der Maarel-Wierink CD, Vanobbergen JN, Bronkhorst EM, Schols JM, de BC. Metaanalysis of dysphagia and aspiration pneumonia in frail elders. J Dent Res 2011; 90:1398-1404. 11. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001; 344:665-671.

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12. Riquelme R, Torres A, El-Ebiary M, de la Bellacasa JP, Estruch R, Mensa J, Fernandez-Sola J, Hernandez C, RodriguezRoisin R. Community-acquired pneumonia in the elderly: A multivariate analysis of risk and prognostic factors. Am J Respir Crit Care Med 1996; 154:1450-1455. 13. Marik PE , Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest 2003; 124:328-336. 14. Rofes L, Arreola V, Romea M, Palomera E, Almirall J, Cabre M, Serra-Prat M, Clave P. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010; 22:851-8, e230. 15. Clave P, de Kraa M, Arreola V, Girvent M, Farre R, Palomera E, Serra-Prat M. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006; 24:1385-1394. 16. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Jr., Musher DM, Niederman MS, Torres A, Whitney CG. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27-S72. 17. Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia 1996; 11:93-98. 18. Gosney M, Punekar S, Playfer JR, Bilsborrow PK, Martin MV. The incidence of oral Gramnegative bacteria in patients with Parkinson's disease. Eur J Intern Med 2003; 14:484-487. 19. Palmer LB, Albulak K, Fields S, Filkin AM, Simon S, Smaldone GC. Oral clearance and pathogenic oropharyngeal colonization in the elderly. Am J Respir Crit Care Med 2001; 164:464-468. 20. Teramoto S, Fukuchi Y, Sasaki H, Sato K, Sekizawa K, Matsuse T. High incidence of aspiration pneumonia in community- and hospital-acquired pneumonia in hospitalized patients: a multicenter, prospective study in Japan. J Am Geriatr Soc 2008; 56:577-579. 21. Kikuchi R, Watabe N, Konno T, Mishina N, Sekizawa K, Sasaki H. High incidence of

OD is a risk factor for CAP in the elderly silent aspiration in elderly patients with community-acquired pneumonia. Am J Respir Crit Care Med 1994; 150:251-253.

23. Gleeson K, Eggli DF, Maxwell SL. Quantitative aspiration during sleep in normal subjects. Chest 1997; 111:1266-1272.

22. Huxley EJ, Viroslav J, Gray WR, Pierce AK. Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am J Med 1978; 64:564-568.

24. Cabre M, Serra-Prat M, Palomera E, Almirall J, Pallares R, Clave P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010; 39:39-45.

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CAPÍTULO 4

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Therapeutic effects of a xanthan gum thickener

Capítulo 4 THE EFFECTS OF A XANTHAN GUM-BASED THICKENER ON THE SWALLOWING FUNCTION OF PATIENTS WITH DYSPHAGIA Laia Rofes, Viridiana Arreola, Rajat Mukherjee, Julie Swanson, Pere Clavé. The effects of a xanthan gum-based thickener on the swallowing function of patients with dysphagia. Aliment Pharmacol Ther 2014; In press. doi:

10.1111/apt.12696

Abstract Background: Increasing bolus viscosity of thin liquids is a basic therapeutic strategy to protect patients with oropharyngeal dysphagia (OD) from aspiration. However, conventional starch thickeners increase postdeglutitive residue. The aim of the study was to assess the therapeutic effect of a new xanthan gum-based thickener, Resource ThickenUp Clear (RTUC) (Nestlé Health Science, Vevey, Switzerland) on patients with OD. Methods: We studied the effect of RTUC using a clinical method and videofluoroscopy (VFS) on 120 patients with OD (66 with stroke, 41 older and 13 with neurodegenerative diseases) and 14 healthy volunteers while swallowing thin liquid, nectar-like, and spoon-thick boluses. We assessed the prevalence of signs of impaired safety and efficacy of swallow and the physiology of the swallow response. Results: Increasing bolus viscosity with RTUC: a) improved safety of swallow demonstrated by a reduction in the prevalence of cough and voice changes in the clinical study and penetrations and aspirations during VFS. Prevalence of aspirations was 12.7% with thin liquid, 7.7% with nectar-like (P<0.01) and 3.4% with spoon-thick (P<0.01) viscosities. Penetration-Aspiration Scale was reduced from 3.24±0.18 at thin liquid to 2.20±0.18 at nectar-like (P<0.001) and to 1.53±0.13 at spoon-thick (P<0.001) viscosities; b) did not enhance pharyngeal residue; c) nectar-like viscosity did not affect bolus velocity nor timing of swallow response; and d) spoon-thick viscosity reduced bolus velocity. Conclusions: RTUC improves the safety of swallow without increasing residue providing a viscositydependent therapeutic effect for patients with OD. At nectar viscosity, the effect is due to intrinsic texture properties, spoon-thick viscosity adding changes in swallow physiology.

Introduction

with neurogenic dysphagia and in the elderly and leads to severe respiratory complications [2]. In stroke patients, OD triplicates the relative risk of pneumonia, which increases to 11 times if the patient presents aspirations [3]. Aspiration pneumonia is associated with a 3-fold increased risk of death compared with stroke patients without pneumonia [4]. In the elderly, OD is also an independent risk factor for the development of lower respiratory tract infections and pneumonia [5-7]. The development of evidence-based treatments that increase safety of swallow and protect patients from aspirations is necessary to avoid respiratory complications and improve morbidity and mortality rates of the dysphagic population [8].

Oropharyngeal dysphagia (OD) is a gastrointestinal motility disorder specifically recognized by the World Health Organization in the International Statistical Classification of Diseases and Related Health Problems ICD-9 and ICD-10 [1]. OD is a highly prevalent clinical condition, present in up to 50% of patients with neurological diseases and in the elderly. Approximately 50-75% of these dysphagic patients present impaired safety of swallow, with bolus penetrations into the laryngeal vestibule and 20-25% tracheobronchial aspirations during swallow response [2]. Delayed laryngeal vestibule (LV) closure is the main mechanism impairing airway protection in patients

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Capítulo 4___________________________________________________________________ One of the basic compensatory interventions in hospitals and long-term care facilities to increase the safety of swallow and avoid aspirations is to thicken liquids. Viscosity is a rheological property that measures the fluid’s internal resistance to flow and the rate of flow per unit of force applied. We have previously described how thickening liquids with starch-based thickeners reduced LV penetrations and tracheobronchial aspirations [9,10] with the consequent reduction in the incidence of aspiration pneumonia rates [11]. It has been proposed that slowing down bolus velocity through the pharynx is the main action mechanism of thickeners to protect against aspirations [12]. However, parallel to its therapeutic effect, enhancing bolus viscosity with starch thickeners increases post-deglutitive oropharyngeal residue, especially in patients with deficient bolus propulsion such as elderly patients and patients with neurodegenerative diseases [2,9,10]. This might increase the risk of post-swallow aspirations [13]. Another disadvantage of starch-based thickened liquids is that they are, in general, not well accepted by patients [14].

Hospital de Mataró (Spain) for swallowing evaluation, were prospectively included in the study. Inclusion criteria were: age more than 18 years, history of swallowing difficulties associated with aging and/or neurological diseases. Exclusion criteria were: allergy to any medication, major respiratory diseases, surgery in the three months prior to the study, background of alcohol or drug dependence or participation in another clinical trial 4 weeks prior. Healthy volunteers (HV) (N=14) were recruited to explore the effect of the xanthan thickener on normal swallow physiology. All participants were informed about the study and gave written consent. The study protocol was approved by the Institutional Review Board of the Hospital de Mataró and was conducted according to the principles and rules laid down in the Declaration of Helsinki and its subsequent amendments. Trial registration: NCT01158313. Demographic, clinical and nutritional characteristics of the study population, as well as severity of dysphagia symptoms, were also collected in all participants.

A new generation of thickeners based on xanthan gum has recently been developed to improve on the therapeutic performance and sensory attributes of the starched–based thickeners. The xanthan gum-based thickeners retain the clarity of clear liquids, possess amylase resistance to keep bolus viscosity stable during saliva contact, are able to thicken a wide range of liquids at different temperatures and maintain stable viscosity over time [15]. However, their clinical therapeutic effect and their mechanisms of action on patients with OD has not been evaluated yet.

Experimental Design

The aim of this study was to assess the therapeutic effect of a xanthan gum-based thickener (Resource ThickenUp Clear, RTUC) on the clinical and videofluoroscopic signs of OD and the swallow function of dysphagic patients to provide researchbased clinical practice [16].

The V-VST was performed as described elsewhere [17]. Briefly, the patients’ ability to swallow boluses of different volumes (5, 10 and 20 mL) and viscosities (thin liquid, nectar-like, spoon-thick) was evaluated in all patients. In addition, in order to evaluate the minimum amount of thickener needed for each patient, the subgroup of patients that presented impaired safety of swallow at nectar viscosity but safe swallow and residue at spoonthick viscosity was evaluated with two additional intermediate viscosities: conservative spoon-thick and honey, using the algorithm described elsewhere [17].

The effect of different levels of viscosity on the clinical signs and symptoms of OD was assessed by a clinical test with high diagnostic accuracy, the Volume-Viscosity Swallow Test (V-VST). The effect on videofluoroscopic signs and the swallow response was assessed by videofluoroscopy (VFS).

Clinical Test

Materials and Methods Study population 120 patients consecutively referred to the Gastrointestinal Physiology Laboratory of the

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Therapeutic effects of a xanthan gum thickener Clinical signs of OD. Signs of impaired efficacy of swallow, such as impaired labial seal, oral residue and piecemeal deglutition (multiple swallows per bolus), symptoms of pharyngeal residue, and signs of impaired safety of swallow, such as changes in voice quality (including wet voice), cough and decrease in oxygen saturation ≥3% (measured with a finger pulse-oximeter, Nellcor OxiMax, Philips Medical Systems, Eindhoven, Netherlands) were evaluated for each swallow [18].

laryngeal vestibule (LV), and UES were measured, GPJ opening being given the time value 0. -1

Bolus kinematics. Mean bolus velocity (m s ) acquired by the bolus during the transit between the GPJ and the UES was also calculated.

Bolus Rheology The viscosities used during V-VST and VFS were prepared according to the descriptors of the National Dysphagia Diet Task Force, 1-50 mPa s for thin liquid, 51-350 mPa s for nectar-like, 3511750 mPa s for honey and conservative spoon20 thick and >1750 mPa s for spoon-thick viscosity . For V-VST studies, thin viscosity was obtained by using mineral water at room temperature, nectarlike viscosity by adding 1.2 g of thickener (Resource ThickenUp Clear, Nestlé Health Science, Vevey, Switzerland) to 100 mL mineral water, and spoon-thick viscosity by adding 6 g of thickener to 100 mL mineral water. Honey viscosity was obtained by adding 2.4 g of thickener, and conservative spoon thick by adding 3.6 g, to 100 mL mineral water. Solutions were prepared 5 min before the test. According to the study protocol, the specific levels of viscosity obtained were 21 mPa s for thin liquids, 238 mPa s for nectar, and 1840 mPa s for EST [17]. For VFS studies, thin viscosity was obtained by mixing 1:1 mineral water and the X-ray contrast Gastrografin (Bayer Hispania SL, Sant Joan Despí, Spain) both at room temperature, nectar viscosity by adding 2.4 g of the thickener to the liquid solution containing the X-Ray contrast and the spoon-thick viscosity by adding 5.4 g of the thickener. Honey viscosity was obtained by adding 3.7 g of thickener to 100 mL of the X-Ray contrast solution and conservative spoon thick by adding 4.4 g. The solutions for VFS studies were prepared 3 hours prior the videofluoroscopic examination to obtain equivalent viscosities to those used during the V-VST [15]. Boluses of 5 mL, 10 mL, and 20 mL of each viscosity were carefully given to patients with a syringe during both V-VST and VFS studies to ensure accurate measurement of bolus volume.

Videofluoroscopy All patients were imaged for the videofluoroscopic study while seated, in a lateral projection which included the oral cavity, pharynx, larynx, and cervical oesophagus. Videofluoroscopic recordings were obtained by using a Super XT-20 Toshiba Intensifier (Toshiba Medical Systems Europe, Zoetermeer, The Netherlands) and recorded at 25 frames/s using a Panasonic AG DVX-100B video camera (Matsushita Electric Industrial Co, Osaka, Japan). Digitization, analysis and measurements of videofluoroscopic images were made using the software Swallowing Observer (Image and Physiology SL, Barcelona, Spain) by an expert clinician not blinded to the viscosity of the bolus. For the videofluoroscopic study, we used the same exploration algorithm as for the V-VST [17]. VFS signs. Impairment in the efficacy of swallow was considered when at least one of the following signs was identified during the VFS study: impaired labial seal, the presence/ absence of oral residue, pharyngeal residue or piecemeal deglutition; and impairment in the safety of swallow was considered when a penetration or an aspiration was detected. The penetrations and aspirations were classified according to the PenetrationAspiration Scale (PAS) [19]. Timing of swallow response. Quantitative measurements of the effect of the thickener (Resource® ThickenUp Clear, Nestlé Health Science, Vevey, Switzerland) on oropharyngeal swallow response were obtained during 5 mL swallows at each viscosity during VFS studies. Timing of opening and closing of glossopalatal junction (GPJ), velopharyngeal junction (VPJ),

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Capítulo 4___________________________________________________________________

Product safety

(Bonferroni adjusted). Statistical significance was accepted if P values were <0.05. Statistical analysis was performed using the stats package in R version 2.15 (www.r-project.org).

Any adverse events (AEs) occurring during the study and until one week after the completion of the study procedures (checked by a telephone call) were documented, assessed for severity and relationship to the study product and classified according to the WHO System Organ Class.

Results Study population The recruitment of participants was carried out between June 2010 and June 2011. Demographic, clinical data and nutritional risk of the study population are described in Table 1. Up to 55% (66) of patients presented OD associated to a previous stroke, 34.2% (41) to aging, and 10.8% (13) to neurodegenerative diseases (mainly Parkinson’s disease (3) and multiple sclerosis (3)). Sixty percent (72) of patients were taking one or more drugs with potential effects on swallow function: 39 were taking antidepressants; 29, anxiolytics; 17, antiepileptics; 10, sedatives and 5, antipsychotics.

Data analysis and statistical methods Qualitative parameters were described by relative and absolute frequencies and were compared by the Fisher’s exact test for independent variables or McNemar’s test for paired variables. Quantitative parameters were described by mean±SEM and compared by the nonparametric Mann Whitney U test or Kruskal-Wallis test for paired variables. Differences between viscosities at each volume was tested using the Cochran’s-Q test. If the P value was less than 5% then each viscosity level was tested against the thin liquid viscosity using McNemar’s test corrected for multiplicity

Table 1. Demographic, clinical and nutritional characteristics of the study population. Healthy volunteers (HV); neurodegenerative diseases (NDD); Mini Nutritional Assessment short form (MNA-SF); Sydney Swallow Questionnaire (SSQ). Patients

Subjects Sex (men) Age (years) Drugs/ day Dysphagia severity (SSQ)

Charlson Index 0 1-2 3-4 ≥5 Nutritional status (MNA-SF) Malnourished (0-7) At risk (8-11) Well nourished (12-14)

HV

Patients

14 57.1% (8) 30.5±6.1

NDD

Stroke

Elderly

120 54.2% (65) 74.4±12.4

13 46.2% (6) 64.0±19.6

66 56.1% (37) 73.5±11.4

41 53.7% (22) 79.6±8.2

0.0±0.0

7.77±3.7

8.31±0.89

7.46±0.42

8.17±0.69

12.1±4.6

460.5±35.5

546.1±69.3

495.2±55.1

375.5±47.5

0 100% (14) 0% (0) 0% (0) 0% (0)

3.04±1.92 10.1% (12) 31.1% (37) 37.0% (44) 21.8% (26) 9.72±2.76

1.54±1.66 17.5% (7) 40.0% (16) 35.0% (14) 7.5% (3) 10.31±3.04

3.82±1.66 0.0% (0) 25.8% (17) 39.4% (26) 34.8% (23) 9.29±2.72

2.25±1.82 38.5% (5) 30.8% (4) 30.8% (4) 0.0% (0) 10.25±2.69

22.9%(27) 48.3% (57) 28.8% (34)

23.1% (3) 38.5% (5) 38.5% (5)

25.8% (17) 53.0% (35) 21.2% (14)

17.9% (7) 43.6% (17) 38.5% (15)

---

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Therapeutic effects of a xanthan gum thickener

Effect of RTUC on clinical signs and symptoms of OD

completed the nectar series without presenting any sign of impaired safety of swallow (P<0.001 vs thin liquid) and up to 95.8% safely completed the spoon thick series (P<0.001 vs nectar-like). Efficacy of swallow. Increasing thin liquid viscosity to spoon-thick improved the labial seal efficacy of dysphagic patients (P<0.05), did not change the prevalence of oral residue or piecemeal deglutition and increased the prevalence of pharyngeal residue symptoms by 18.9% (P<0.05) (Figure 1). Intermediate viscosities. Conservative spoon-thick viscosity was administered to 31 patients with impaired safety at nectar and safe swallow but residue at spoon-thick viscosity. Of those, 6 presented signs of impaired safety and 22 symptoms of pharyngeal residue. Honey viscosity was evaluated in 27 patients; 5 of them presented signs of impaired safety and 14 reported pharyngeal residue.

Healthy volunteers. Safety of swallow. Only one healthy volunteer presented a voice change after the deglutition of 20 mL of thin liquid and 20 mL of nectar but not at spoon-thick viscosity. None of the HV presented cough or decreased oxygen saturation at any of the studied viscosities. Efficacy of swallow. All the HV presented adequate labial seal and were able to swallow all the boluses offered in a single swallow. One healthy volunteer presented oral and pharyngeal residue at spoonthick viscosity. Patients. Prevalence of clinical signs of impaired efficacy and safety of swallow in patients with OD at each viscosity series was very high and is depicted in Figure 1. Safety of swallow. Only 20.8% of patients were able to complete the thin liquid series safely. Up to 60.8% of patients

Figure 1. Prevalence of clinical signs of safety and efficacy of swallow for each bolus volume and viscosity in patients with oropharyngeal dysphagia. Safety of swallow was expressed as the percentage of patients that could swallow without voice changes, cough or oxygen desaturation for each bolus volume and viscosity. *P<0.05, **P<0.01, ***P<0.001 vs thin liquid viscosity.

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Capítulo 4___________________________________________________________________

Effect of RTUC on videofluoroscopic signs of OD

significant penetrations (scores 3-5) was reduced from 35.3% during thin liquid series to 13.7% at nectar-like viscosity (P<0.01) and to 9.3% at spoon-thick (P<0.01). Prevalence of patients with aspirations (scores 6-8) was reduced from 12.7% during thin liquid series to 7.7% at nectar (P<0.01) and to 3.4% at spoon-thick (P<0.01). The mean score of the PAS was reduced from 3.24±0.18 at thin liquid to 2.20±0.18 at nectar (P<0.001) and to 1.53±0.13 at spoon-thick (P<0.001). Efficacy of swallow. At thin liquid viscosity, 12.6% of patients presented significant oral residue and 14.6% presented pharyngeal residue. Increasing bolus viscosity with the xanthan gum thickener did not significantly modify the prevalence of oral, vallecular nor pyriform sinus residue (P>0.05) (Figure 2). Intermediate viscosities. Conservative spoon-thick viscosity was tested in 21 patients with impaired safety at nectar and safe swallow with residue at spoon-thick viscosity. Of those, 5 still presented penetrations; 10, oral residue and 17, pharyngeal residue. Honey viscosity was also evaluated in 21 patients; 3 of them presented penetrations at the laryngeal vestibule, 1 presented an aspiration. Oral residue was present in 10 patients and pharyngeal residue in 17.

Healthy volunteers. Safety of swallow. Two HV presented non-pathological penetrations into the LV during the deglutition of thin liquid swallows (score 2 in the PAS) while none of them presented penetrations nor aspirations during the deglutition of nectar and spoon-thick viscosities. Efficacy of swallow. Two of the HV presented mild oral residue at liquid and spoon-thick viscosities and three at nectar-like viscosity. None of them presented pharyngeal residue at any of the viscosities tested. Patients. Prevalence of videofluoroscopic signs of impaired efficacy and safety of swallow is shown in Figure 2. Safety of swallow. Increasing bolus viscosity with the xanthan gum thickener significantly increased the prevalence of patients able to swallow safely from 23.72% at thin liquid viscosity series, to 55.08% at nectar viscosity (P<0.001) and to 84.74% at spoon-thick viscosity series (P<0.001). Figure 3 showed distribution of patients according to the maximum score presented in the PAS at each viscosity. It should be noted that prevalence of patients with clinically

Figure 2. Prevalence of videofluoroscopic signs of safety and efficacy of swallow for each bolus volume and viscosity in patients with oropharyngeal dysphagia. Safety of swallow was expressed as the percentage of patients that could swallow without signs of contrast entering the laryngeal vestibule or traversing the vocal folds for each bolus volume and viscosity. *P<0.05, **P<0.01, ***P<0.001 vs thin liquid viscosity.

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Therapeutic effects of a xanthan gum thickener P<0.001) during 5 mL liquid swallow. Considering all patients with OD, increasing bolus viscosity to nectar and spoon-thick viscosities did not significantly affect LV closure time (363.1±11.2 ms at nectar viscosity and 434.8±22.9 ms at spoonthick, P>0.05 vs thin liquid) or total duration of swallow response (959.3±17.2 ms at nectar viscosity and 1027.1±26.03 ms at spoon-thick, P>0.05 vs thin liquid). However, time to UES opening was increased at spoon-thick viscosity to 427.5±24.3 ms (P=0.009 vs thin liquid). Figure 4 shows time to LV closure of patients stratified according to the safety of their swallow at each viscosity (presence of penetrations or aspirations). Patients with impaired safety presented a delayed LV closure compared to patients with safe swallow in all three viscosities (P<0.05). Patients with safe swallow at thin liquid and nectar-like viscosities had similar timing to airway closure (386.4±26.8 ms at thin liquid and 350.8±11.8 ms at nectar viscosity, P>0.05), but at spoon-thick viscosity, presented a later time to LV closure (427.8±24.5 ms, P<0.01) and UES opening.

Figure 3. Relative frequencies of patients according to the maximum score presented in the Penetration-Aspiration Scale in each viscosity series.

Effect of RTUC physiology

on

oropharyngeal

Healthy volunteers Timing of swallow response. Total duration of swallow (time from GPJ opening to LV opening) of HV during 5 mL thin liquid swallow was 742.9±29.9 ms. The airway closed at 171.4±12.2 ms and the UES opened at 220.0±16.6 ms. Increasing bolus viscosity to nectar did not significantly affect time to LV closure (174.3±11.6 ms, P>0.05) and opening (722.9±22.4 ms, P>0.05) nor UES opening (234.3±8.2 ms, P>0.05). However, increasing bolus viscosity to spoon-thick delayed time to LV closure and UES opening to 230.8±11.2 ms (P=0.003 vs thin liquid) and 283.1±11.5 ms (P=0.003 vs thin liquid) respectively, but not time to LV opening (P =0.261 vs thin liquid).

Bolus Kinematics. The mean velocity of a 5 mL thin liquid bolus (0.248±0.010 m/s) was not changed by increasing bolus viscosity to nectar (0.238±0.010 m/s, P=0.438), but was significantly slowed at spoon-thick viscosity (0.214±0.010 m/s, P=0.019 vs thin liquid).

Product safety A total of 37 minor AEs occurred in 34 (25.4%) persons during the study and the follow-up period, 30 (25.0%) in patients and 4 (28.6%) in HV. Of these, 36 AEs were gastrointestinal system disorders, specifically, 33 episodes of loose stools, 1 of nausea, 1 of vomiting and 1 of bloating were registered. The majority of them were mild and not considered treatment related. There was one serious adverse event (bronchoaspiration) that was considered unlikely to be related to the study product but related to the study procedure.

Patients Timing of swallow response. Overall, patients included in the study presented prolonged swallow response (988.5±21.2 ms, P<0.001 vs HV) and delayed airway closure (399.6±19.3 ms, P<0.001 vs HV) and UES opening (328.7±14.3 ms,

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Capítulo 4___________________________________________________________________

Figure 4. Laryngeal vestibule closure time of healthy volunteers and patients included in the study during 5 mL swallows, stratified according to the safety of swallow. #P<0.05 vs patients with safe swallow; **P<0.01.

Discussion

care for dysphagic patients [14]. Despite widespread use and good acceptance, there are few studies objectively assessing the therapeutic effect of thickeners and the level of evidence is low [21]. In addition, there are many thickeners and gelling agents commercially available, all presenting different components and rheological properties with potentially different therapeutic effects. Thus, the objective assessment of the real effectiveness of these agents in specific clinical trials is crucial for adequate management of dysphagic patients and to ensure airway protection to avoid respiratory complications. This study shows, for the first time, the strong viscositydependent therapeutic effect of a new xanthan gum-based thickener providing research-based evidence of its clinical usefulness in OD management.

The main conclusion of this study is that the new xanthan gum-based thickener, RTUC, presents a strong viscosity-dependent therapeutic effect in patients with OD by improving the safety of swallow without increasing oropharyngeal residue. We found that it is possible to provide safe swallow to more than 84% of patients with OD by using RTUC at spoon-thick viscosity irrespective of the bolus volume offered to the patient. Moreover, prevalence of oropharyngeal residue after deglutition of thickened boluses is significantly lower than those reported in previous studies using starched-based thickeners [2,9,18] an advantage of xanthan gum thickeners versus conventional agents. Thickening of fluids is a basic strategy in OD management, prescribed to the majority of dysphagic patients [14]. Even though a lack of consensus exists in terms of rheological properties, terminology, descriptors and definitions of modified fluids, thickening liquids is perceived as an effective strategy by health professionals providing

In this study we included patients representing the most prevalent populations and phenotypes of patients at risk for OD that can be found in primary care, general hospitals and nursing homes such as the elderly and patients with stroke and neurodegenerative diseases. Prevalence of - 90 -

Therapeutic effects of a xanthan gum thickener malnutrition, co-morbidities and polymedication with potential effects on swallowing function among our population was very high, putting them at high risk for developing life-threatening respiratory complications if not managed properly. We previously found that 80% of hospital readmissions for aspiration pneumonia in elderly patients were attributable to oropharyngeal dysphagia [8]. Oneyear mortality rates of our elderly patients with OD are above 50% [2]. The RTUC was also evaluated in a group of HV to provide normality values and to obtain data on the effect of the thickener on normal swallow response and its safety profile.

with different concentrations of xanthan gum [22]. In contrast, previous studies evaluating the effect of starch thickeners [2,9,18], reported an important increase in pharyngeal residue at spoon-thick viscosities. Post-deglutitive residue can be easily aspirated in the inhalation process and put the patient at risk for respiratory complications. Therefore, the highest protection offered by the xanthan gum-based thickeners compared with the starch thickeners, together with the absence of pharyngeal residue increment, confers to this new generation of thickeners a greater therapeutic value.

In our study, the therapeutic effect of the thickener RTUC was determined by means of a validated clinical test (V-VST) and a videofluroscopic study. In the clinical study we observed that increasing bolus viscosity reduced prevalence of cough and voice changes associated to swallow, indicating a strong effect on clinical signs of safety of swallow. This effect was confirmed in the videofluoroscopic study, as a viscosity-dependent reduction in the prevalence of penetrations and aspirations was clearly observed. This therapeutic effect on safety of deglutition exerted by RTUC in this study is higher to that we observed using boluses of similar levels of viscosity obtained by starch thickeners in previous studies in patients with neurological diseases (non-progressive and neurodegenerative) [9], a mixed cohort of patients including head and neck diseases [18] and in frail elderly patients [2]. In terms of efficacy of deglutition, we observed in the clinical study that pharyngeal residue increased at spoon-thick viscosity when compared with thin liquids. However, this effect was not confirmed by the videofluoroscopy. This discrepancy could be explained because in the clinical study, the pharyngeal residue is not a sign directly observed by the clinician but is assessed as a symptom reported by the patient (feeling that the bolus sticks in the throat). Pharyngeal and laryngeal sensory abnormalities, often described in dysphagic patients, could contribute to this symptom. Using videofluoroscopy, we did not observe any significant enhancement in vallecular or pyriform sinus residue by increasing bolus viscosity. These results agree with a previous study in HV that did not find any increase of pharyngeal residue by increasing bolus viscosity

We observed that thin and nectar-like liquids moved more quickly through the pharynx than boluses at spoon-thick viscosity both in HV and in patients. In HV, the timing of reconfiguration of oropharyngeal structures from a respiratory pathway to a digestive pathway adapted to the bolus transit, and the increased bolus velocity of thin and nectar-like liquids was associated with an earlier LV closure and UES opening times. Dysphagic patients presented delayed airway protection (LV closure time), specifically prolonged in patients with impaired safety, responsible for the observed penetrations and aspirations into the airways. It has been proposed that slowing down bolus flow velocity through the pharynx confers thickeners their main therapeutic effect [12]. However, we have observed that a moderate level of viscosity, such as nectar-like viscosity, strongly improved airway protection without modifying bolus velocity nor timing of the oropharyngeal swallow response compared to thin liquids. Therefore, RTUC is able to improve swallow safety without producing any change in swallow physiology, suggesting that the intrinsic proprieties of the thickened bolus are responsible for the observed therapeutic effect at this level of viscosity. We have also observed that, at spoon-thick viscosity, bolus velocity is reduced, suggesting that at high viscosity levels, the therapeutic effect of RTUC depends not only on its intrinsic texture properties, but also to additional effects produced by changes in swallow physiology. Looking at the other timing related events, we observed that UES opening time was delayed at spoon-thick viscosity. As the UES requires bolus pressure in order to open, the reduced velocity of spoon-thick viscosities that thus

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Capítulo 4___________________________________________________________________ http://apps.who.int/classifications/icd10/brow se/2010/en#/R13

takes more time to reach the sphincter, delay UES opening time. Total duration of swallow response (time from GPJ opening to LV opening) was not affected by any level of bolus viscosity in HV nor in patients.

2. Rofes L, Arreola V, Romea M et al. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010; 22: 851-8, e230.

The therapeutic effect of xanthan gum thickeners versus starch thickeners at similar levels of viscosity should be further explored by comparative clinical studies, and be based not only on rheological characteristics such as bolus viscosity but also on textural properties such as hardness, cohesiveness, adhesiveness or gumminess, especially at mid-levels of viscosity. It has been reported in post-stroke dysphagic patients that semisolids with high cohesiveness were more likely to accumulate in the pharynx while high gumminess could lead to tracheobronchial aspirations [23]. However, data on the effect of these textural properties on the safety and efficacy of swallow is scarce and further studies are necessary to characterize their influence on the effect of thickeners. Finally, results of this study show that RTUC is a safe product with low incidence of AEs. Most of the AEs affected the gastrointestinal tract, were mild and probably related to the X-Ray contrast that causes a wellknown osmotic laxative effect on small bowel and enhances colonic motility.

3. Martino R, Foley N, Bhogal S et al. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005; 36: 2756-63. 4. Katzan IL, Cebul RD, Husak SH, Dawson NV, Baker DW. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003; 60: 620-5. 5. Serra-Prat M, Palomera M, Gomez C et al. Oropharyngeal dysphagia as a risk factor for malnutrition and lower respiratory tract infection in independently living older persons: a population-based prospective study. Age Ageing 2012; 41: 376-81. 6. Cabre M, Serra-Prat M, Palomera E et al. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010; 39: 39-45. 7. Almirall J, Rofes L, Serra-Prat M et al. Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly. European Respiratory Journal 2013; 41: 923-8.

In conclusion, increasing bolus viscosity with the xanthan gum thickener RTUC exerts a strong viscosity-dependent therapeutic effect on patients with OD by improving the safety of swallow without increasing oropharyngeal residue, an advantage of this new generation of xanthan gum thickeners over conventional agents. Our study also suggests that RTUC exerts its therapeutic effect through two sequential mechanisms: at nectar-like viscosity the therapeutic effect relies on the intrinsic rheological or texture properties of the thickener whereas with spoon-thick viscosity, significant changes in swallow physiology also occur.

8. Cabre M, Serra-Prat M, Force L et al. Oropharyngeal Dysphagia is a Risk Factor for Readmission for Pneumonia in the Very Elderly Persons: Observational Prospective Study. J Gerontol A Biol Sci Med Sci 2014;69:330-7. 9. Clave P, de Kraa M, Arreola V et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006; 24: 1385-94. 10. Bhattacharyya N, Kotz T, Shapiro J. The effect of bolus consistency on clysphagia in unilateral vocal cord paralysis. Otolaryngology-Head and Neck Surgery 2003; 129: 632-6.

References 1. World Health Organization. ICD-10 Version:2010 [homepage on the internet]. Geneva: World Health Organization. 2010 [cited 2013 Aug 13]; Available from:

11. Groher ME. Bolus Management Aspiration Pneumonia in Patients

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and with

Therapeutic effects of a xanthan gum thickener Pseudobulbar Dysphagia. Dysphagia 1987; 1: 215-6.

18. Clave P, Arreola V, Romea M et al. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008; 27: 806-15.

12. Dantas RO, Kern MK, Massey BT et al. Effect of Swallowed Bolus Variables on Oral and Pharyngeal Phases of Swallowing. American Journal of Physiology 1990; 258: G675-G681.

19. Rosenbek J, Robbins J, Roecker E. A penetration-aspiration scale. Dysphagia 1996; 11: 93-8.

13. Perlman AL, Booth BM, Grayhack JP. Videofluoroscopic predictors of aspiration in patients with oropharyngeal dysphagia. Dysphagia 1994; 9: 90-5.

20. The National Dysphagia Diet Task Force. National Dysphagia Diet: Standardization for Optimal Care. Chicago: American Dietetic Association; 2002.

14. Garcia JM, Chambers E, Molander M. Thickened liquids: Practice patterns of speech-language pathologists. American Journal of Speech-Language Pathology 2005; 14: 4-13.

21. Speyer R, Baijens L, Heijnen M, Zwijnenberg I. Effects of therapy in oropharyngeal dysphagia by speech and language therapists: a systematic review. Dysphagia 2010; 25: 40-65.

15. Popa Nita S, Murith M, Chisholm H, Engmann J. Matching the Rheological Properties of Videofluoroscopic Contrast Agents and Thickened Liquid Prescriptions. Dysphagia 2013; 28: 245-52.

22. Bogaardt HCA, Burger JJ, Fokkens WJ, Bennink RJ. Viscosity is not a parameter of postdeglutitive pharyngeal residue: Quantification and analysis with scintigraphy. Dysphagia 2007; 22: 145-9.

16. Hjorland B. Evidence-Based Practice: An Analysis Based on the Philosophy of Science. Journal of the American Society for Information Science and Technology 2011; 62: 1301-10.

23. Momosaki R, Abo M, Kobayashi K. Swallowing Analysis for Semisolid Food Texture in Poststroke Dysphagic Patients. Journal of Stroke & Cerebrovascular Diseases 2013; 22: 267-70.

17. Rofes L, Arreola V, Clave P. The volumeviscosity swallow test for clinical screening of Dysphagia and aspiration. Nestle Nutr Inst Workshop Ser 2012; 72: 33-42.

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CAPÍTULO 5

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Capsaicinoids improve swallow in older patients with OD

Capítulo 5 NATURAL CAPSAICINOIDS IMPROVE SWALLOW RESPONSE IN OLDER PATIENTS WITH OROPHARYNGEAL DYSPHAGIA Laia Rofes, Viridiana Arreola, Alberto Martin, Pere Clavé. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia. Gut 2013; 62(9):1280-7.

Abstract Background: There is no pharmacological treatment for oropharyngeal dysphagia (OD). The aim of this study was to compare the therapeutic effect of stimulation of oropharyngeal transient receptor potential vanilloid type 1 (TRPV1) with that of thickeners in older patients with OD. Methods: A clinical videofluoroscopic non-randomised study was performed to assess the signs of safety and efficacy of swallow and the swallow response in: a) 33 patients with OD (75.94±1.88 years) while swallowing 5, 10 and 20 mL of liquid (20.4 mPa.s), nectar (274.4 mPa.s), and pudding (3930 mPa.s) boluses, b) 33 patients with OD (73.94±2.23 years) while swallowing 5, 10 and 20 mL nectar boluses, and two series of nectar boluses with 150 µM capsaicinoids and c) 8 older controls (76.88±1.51 years) while swallowing 5, 10 and 20 mL nectar boluses. Results: Increasing bolus viscosity reduced the prevalence of laryngeal penetrations by 72.03% (P<0.05), increased pharyngeal residue by 41.37% (P<0.05), delayed the upper esophageal sphincter opening time and the larynx movement and did not affect the laryngeal vestibule closure time and maximal hyoid displacement. Treatment with capsaicinoids reduced both penetrations by 50.00% (P<0.05) and pharyngeal residue by 50.00% (P<0.05) and shortened the time of laryngeal vestibule closure (P<0.001), upper esophageal sphincter opening (P<0.05) and maximal hyoid and laryngeal displacement. Conclusion: Stimulation of TRPV1 by capsaicinoids strongly improved safety and efficacy of swallow and shortened the swallow response in older patients with OD. Stimulation of TRPV1 might become a pharmacologic strategy to treat OD.

Introduction Oropharyngeal dysphagia (OD) is a major complaint among the elderly. It affects more than 20% of independently-living older persons[1] and up to 5678% of elderly institutionalized patients.[2] OD is a severe condition in older persons and may cause two groups of clinically relevant complications: (i) a decrease in the efficacy of deglutition, leading to malnutrition and/or dehydration in up to 33% of patients and (ii) a decrease in the safety of deglutition, resulting in laryngeal vestibule penetrations or in tracheobronchial aspirations, which can lead to aspiration pneumonia with an associated mortality of up to 50%.[3, 4, 5] Currently, the standard of care for the majority of these older patients suffering from OD is very poor as most of

them are not even diagnosed and do not receive any treatment for this condition. An overall decrease in the sensitivity of the pharyngeal and supraglottic areas has been described in elderly persons[6, 7] and also in stroke patients with OD, much more marked in those with aspiration.[8] A lack of afferent myelinated nerve fibers in the superior laryngeal nerve has been described in the elderly, and may be related to agerelated sensorial dysfunction of the upper aerodigestive tract.[9, 10] In stroke patients, the deficit could be caused by the disruption of the connection of the sensory afferents with the cortex and the brainstem. These sensory deficits are involved in the pathophysiology of the impaired swallow response of these dysphagic patients[11] and predispose to aspiration and aspiration

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Capítulo 5___________________________________________________________________ pneumonia. We hypothesized that enhanced oropharyngeal stimuli might improve the afferent sensorial input to the central pattern generator in the swallowing centre of the brainstem, achieving earlier the threshold to trigger the swallow response.[12] Moreover, repetitive sensorial stimuli may reorganize the motor cortex, facilitating deglutition.[13,14] The most effective afferent areas to trigger the swallow response are the anterior faucial pillars, the palatopharyngeal arch and the posterior pharyngeal wall (innervated by the pharyngeal branch of the glossopharyngeal nerve, GPNph, IX cranial nerve), and the epiglottis and the aryepiglottic arch (innervated by the superior laryngeal nerve, SLN, branch of the X cranial nerve).[15] These afferents are sensitive to mechanical stimuli, to changes in temperature and to chemical stimuli, and express the polymodal Transient Receptor Potential Vanilloid 1 (TRPV1).[16] Afferents project to the supramedullar structures and to the nucleus tractus solitarius in the brainstem, allowing the involuntary onset of swallow response and modulating volitional swallowing.[15] Several clinical studies found TRPV1 agonists such as piperine (main component of Piper nigrum)[14] and capsaicin (component of several species of Capsicum sp)[17-19] reduced the time to swallowing onset in elderly patients with dysphagia. Other TRPV1 agonists such as acid[20] or high temperature[21] also showed positive clinical results in improving swallow in dysphagic patients. In addition, natural capsaicinoids increased the amplitude and velocity of esophageal body peristalsis[22] and we believe they could be a safe and effective alternative to test the effects of TRPV1 agonists on dysphagic patients. However, the specific effects of natural capsaicinoids on the physiology of the swallow response are not known, nor their possible therapeutic potential among patients with OD compared with other established treatments. The aim of our study was to explore, in a clinical study, the physiological and therapeutic effects of natural capsaicinoids added to the alimentary bolus, in order to assess its potential as a pharmacological tool to treat patients with OD.

Materials and Methods Patients We designed a non-randomised videofluoroscopic study to assess and compare the effects of capsaicinoids on the deglutition of older patients with mild OD with the effects of standard treatment with thickeners[23]. The study was carried out in the Gastrointestinal Physiology Lab and in the Radiology Unit of the Hospital de Mataró (Spain). All participants were recruited from the Acute Geriatric Unit and from the Neurology Unit of the Hospital de Mataró. The volume-viscosity swallow test (VVST) was used for bedside clinical screening of OD[24] and the Sydney Swallowing Questionnaire was used to clinically assess the severity of the symptoms of dysphagia.[25] We studied: a) 8 older controls (76.88±1.51 years, 5 men) without symptoms of OD and with a negative VVST, and b) 66 older patients (74.94±1.45 years, 36 men) with mild OD (clinical complaints and positive VVST) associated to aging (n=20), neurodegenerative diseases (n=16) or chronic OD following stroke (n=30). The sample size was calculated in a bilateral test for a statistical power of 80%, alpha error 0.05, expected reduction of laryngeal vestibule closure time of 100 ms, expected standard deviation of 130 ms and expected loss to follow up of 20%. Patients with severe clinical signs of aspiration including oxygen desaturation ≥3% were not included in this initial study. The study protocol was approved by the Institutional Review Board of the Hospital de Mataró and was conducted according to the principles and rules laid down in the Declaration of Helsinki and its subsequent amendments. Trial registration: ISRCTN31088564.

Videofluoroscopic procedures All patients were imaged for the videofluoroscopic study while seated, in a lateral projection which included the oral cavity, pharynx, larynx, and cervical esophagus. Videofluoroscopic recordings were obtained by using a Super XT-20 Toshiba Intensifier (Toshiba Medical Systems Europe, Zoetermeer, The Netherlands) and recorded at 25 frames/s using a Panasonic AG DVX-100B video camera (Matsushita Electric Industrial Co, Osaka,

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Capsaicinoids improve swallow in older patients with OD Japan). Older controls were studied during the deglutition of a series of one bolus of 5 mL, one bolus of 10 mL and one bolus of 20 mL at nectar viscosity (274.42±13.14 mPa s). Patients with oropharyngeal dysphagia were divided into 2 treatment groups: a) 33 patients (75.94±1.88 years, 20 men) were studied during the deglutition of a series of one bolus of 5 mL, one bolus of 10 mL and one bolus of 20 mL at nectar viscosity, a series of liquid (20.40±0.23 mPa s) and a series of pudding viscosity (3931.23±166.15 mPa s) with the same bolus volumes; b) 33 patients (73.94±2.23 years, 16 men) were studied during the deglutition of one series of nectar boluses (one bolus of 5 mL, one bolus of 10 mL and one bolus of 20 mL) (pH = 6.35±0.026) and two series of nectar boluses of the same volumes supplemented with a capsaicinoid concentration of 150 µM (pH = 3.36±0.01), each patient acting as his or her own control. The two supplemented bolus series were administered 10 min apart and a sensitization process was conducted on each patient by administering two 5 mL boluses also supplemented with 150 µM capsaicinoids 5 min before the first treatment bolus series. A 9-point visual analogue scale was administered to patients to assess the acceptability of the offered boluses. Punctuations range from 1 (extremely unpleasant) to 9 (extremely pleasant) being the point 5 “neither pleasant nor unpleasant”. Liquid viscosity was obtained by mixing 1:1 mineral water and the X-ray contrast Gastrografin (Berlimed SA, Madrid, Spain), nectar viscosity by adding 3.5 g of the thickener Resource ThickenUp (Nestlé Nutrition, Barcelona, Spain) to 100 mL of liquid solution and pudding viscosity by adding 8 g of the thickener. Bolus density for liquid was 1.19±0.007 g -1 -1 mL , nectar 1.23±0.007 g mL , and pudding -1 1.27±0.001 g mL . Boluses were carefully offered to patients with a syringe.

Drugs Capsaicinoid concentration in capsaicinoid sauce (McIlhenny Co, Avery Island, LA, USA) was determined using liquid chromatography (AOAC 995.03 method), and a concentration of 185.5 µg/g was obtained. Final concentrations were obtained by dissolution of the capsaicinoid sauce in the nectar bolus.

Videofluoroscopic signs Videofluoroscopic signs of safety and efficacy of deglutition were identified accordingly to previously accepted definitions:[3,23] impaired efficacy of a swallow act was identified when one or more of the following signs were detected: decreased lingual control or bolus propulsion, presence of oral, vallecular or sinus pyriform residue or impaired upper esophageal sphincter (UES) opening; similarly, impaired safety of a swallow act was identified when a penetration and/or an aspiration occurred. Penetration was defined as the entrance of swallowed material into the laryngeal vestibule and aspiration as the passage of this material below the vocal folds.

Oropharyngeal swallow response Digitization, analysis and measurements of videofluoroscopic images were made using the software Swallowing Observer (Image and Physiology SL, Barcelona, Spain).[3,23,24] Quantitative measurements of oropharyngeal swallow response were obtained during 5 mL swallows: a) Oropharyngeal reconfiguration: timing of opening and closing of glossopalatal junction (GPJ), velopharyngeal junction (VPJ), laryngeal vestibule (LV), and UES were measured, GPJ opening being given the time value 0.[26] b) Hyoid motion: vertical and anterior hyoid position was determined in an xy coordinate system in each frame: the anterior-inferior corner of C3 was used as the origin, and the vertical axis was defined by a line connecting the anterior inferior corners of C3 and C5.[26] c) Laryngeal movement: maximal vertical and anterior displacement of the larynx was also determined. The position of the anterior superior corner of the supraglottic air column was referenced to the xy coordinate system.[27] d) -1 Bolus kinematics: maximal velocity (m s ) acquired by the bolus prior to entering the UES was evaluated.[3]

Statistical methods Categorical variables were described as percentages (number of deglutitions with specific signs of impaired safety and/or efficacy of swallow versus total number of deglutitions) and compared

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Capítulo 5___________________________________________________________________ by the Fisher’s exact test. Quantitative parameters were described by mean ± SEM. Comparisons between groups were assessed by the nonparametric Mann–Whitney U-test and comparisons within each group were assessed by the nonparametric Wilcoxon matched pairs test. Hyoid profiles were compared by two-way ANOVA analysis. A sub-analysis in patients with previous stroke was also performed to evaluate the effect of capsaicinoids on this specific population. Statistical significance was accepted if P values were <0.05. Statistical analysis was performed using GraphPad Prism 4.01 (San Diego, CA, USA).

Results Patient demographics assessment of OD

and

clinical

Age, sex, and clinical characteristics of patients included in both group of treatments were very similar (Table 1). Older controls did not present clinical signs of OD. The prevalence of clinical signs of impaired safety and/or efficacy of swallow and clinical severity scores for OD were very homogeneous between both branches of

treatments: up to 65.38% of patients treated with thickeners and 54.84% (P=0.588) of patients treated with capsaicinoids presented signs of both impaired safety and efficacy of swallow, 7.69% of patients treated with thickeners and 16.13% (P=0.436) of patients treated with capsaicinoids showed impairment only in safety and 26.9% of patients treated with thickeners and 29.03% (P=1.00) of patients treated with capsaicinoids showed impairment only in efficacy. The Sydney Swallow Questionnaire score for severity of OD was low for older controls (115.00±80.69) and was significantly higher in older patients with dysphagia (372.2±43.67, P<0.01). Assessing the scores of the two treatment groups, non significant difference were found between dysphagic patients treated with thickeners (432.90±73.60) and capsaicinoids (315.15±47.97, P=0.40).

Acceptability of the boluses Punctuations of the visual analogue scale were 4.54±0.227 for the nectar control bolus and 4.37±0.245 for the capsaicinoids supplemented bolus (P=0.628).

Table 1: Patient demographics and clinical characteristics. Data presented as number of cases (percentage), except *mean±SEM. Thickener group (n=33)

Capsaicinoids group (n=33)

P value

Age (years)

75.94±1.88*

73.94±2.23*

0.497

Sex (men)

16 (48.48%)

20 (60.61%)

0.480

Stroke

15 (45.45%)

15 (45.45%)

1.000

Aging

6 (18.18%)

4 (12.12%)

0.733

Chronic pulmonary diseases

3 (9.09%)

4 (12.12%)

1.000

Multiple sclerosis

3 (9.09%)

3 (9.09%)

1.000

Alzheimer disease

0 (0.00%)

1 (3.03%)

1.000

Parkinson disease

3 (9.09%)

3 (9.09%)

1.000

Dementia

2 (6.06 %)

1 (3.03%)

1.000

Myasthenia gravis

1 (3.03%)

1 (3.03%)

1.000

Inclusion body myositis

0 (0.00%)

1 (3.03%)

1.000

Dysphagia related pathology:

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Capsaicinoids improve swallow in older patients with OD

Effect of capsaicinioids on videofluoroscopic signs of efficacy and safety of swallow All older controls presented a safe and efficacious swallow at videofluoroscopy. In contrast, elderly patients with dysphagia included in both groups of treatment presented a high prevalence of videofluoroscopic signs of impaired safety and/or efficacy of swallow that are summarized in Figure 1. There were no significant differences in the prevalence of videofluoroscopic signs of impaired safety or efficacy of swallow at nectar viscosity of both groups. a) Increasing bolus viscosity to pudding strongly reduced prevalence of penetrations (-72.03%, P<0.05) and significantly increased oral residue (+20.89%, P<0.05) as well as pharyngeal residue in vallecula and pyriform sinus (+41.37%, P<0.05). Nectar viscosity also reduced the prevalence of penetrations (-80.91% vs liquid viscosity, P<0.05). b) Treatment with capsaiciniods strongly reduced the prevalence of penetrations (-50.00%, P<0.05) and also pharyngeal residue (-50.00%, P<0.05), without significant changes in oral residue (Figure 1). Moreover, prevalence of impaired tongue propulsion, impaired glossopalatal seal closure and impaired UES opening were not changed by either treatment (data not shown).

Effect of capsaicinoids oropharyngeal swallow response

on

a) Oropharyngeal reconfiguration: Total duration of swallow response in older controls (GPJ openingLV opening) for 5 mL nectar boluses was 0.895±0.038 s and the interval for oropharyngeal reconfiguration from a respiratory to a digestive pathway was very short: it takes 0.230±0.040 s for LV closure. Patients with OD in both treatment groups presented a significant delay in the reconfiguration phase, LV closure time was >0.390 s (P<0.05 vs older controls) and there were no significant differences in the oropharyngeal swallow response times at nectar viscosity of both groups. Changes in bolus viscosity did not affect total duration of swallow response nor delayed timing of LV closure, but increasing bolus viscosity to pudding delayed UES opening in patients with OD.

Figure 1: Videofluoroscopic signs. Effect of thickeners (white bars) and capsaicinoids 150 µM (grey bars) on the prevalence of main signs of efficacy (A, oral residue and B, pharyngeal residue) and safety (C, laryngeal vestibule penetrations) of swallow. Prevalence is expressed as the mean of subjects who presented the sign at each viscosity versus total number of subjects ± SEM.*P<0.05.

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Capítulo 5___________________________________________________________________ In contrast, bolus supplementation with capsaicinoids greatly shortened time to LV closure (from 0.410±0.024 s to 0.296±0.026 s, P<0.001) and time to UES opening (from 0.372±0.024 s to 0.299±0.020 s, P<0.05) without affecting total duration of swallow response (1.00±0.036 s at nectar bolus vs 0.901±0.026 s with capsaicinoids, P=0.095) (Figure 2). b) Hyoid motion: Hyoid movement was affected by both thickeners and capsaicinoids. Increasing bolus viscosity to pudding reduced the hyoid movement profile but did not significantly change the timing of maximal and vertical hyoid excursion. In contrast, capsaicinoids caused an overall improvement in the hyoid movement profile and patients with this treatment reached the maximum vertical extension earlier (0.493±0.040 s at nectar bolus vs 0.354±0.034 s at bolus with capsaicinoids, P<0.05) (Figures 3 and 4). c) Laryngeal movement: Neither bolus viscosity nor capsaicinoids affected the maximal vertical and anterior extension achieved by the larynx (data not shown). Thickeners (pudding viscosity) delayed the maximal vertical and anterior laryngeal displacement, whereas capsaicinoids shortened this time (Figure 4). d) Bolus kinematics: Bolus velocity was reduced -1 by pudding viscosity (0.342±0.037 m s vs -1 0.445±0.040 m s in nectar bolus P<0.05) and -1 enhanced by capsaicinoids (0.424±0.030 m s vs -1 0.340±0.025 m s in nectar control bolus, P<0.01).

Stroke patients The supplementation of the alimentary bolus with capsaicinoids also improved the efficacy and the safety of swallow of the subgroup of elderly patients with previous stroke (n=15): pharyngeal residue was reduced by -93.81% (P<0.01), prevalence of penetrations by -47.39% (P=0.09), time of LV closure by -19.5% (P=0.09) and time of maximal vertical extension of the hyoid bone by -40.4% (P<0.05).

Figure 2: Oropharyngeal reconfiguration. Timing of main events of the oropharyngeal swallow response during 5 mL swallows in healthy elderly (black) and elderly patients with dysphagia. Effect of thickeners (white) and capsaicinoids (grey) on the laryngeal vestibule closure time (A), upper esophageal sphincter opening time (B) and laryngeal vestibule opening time (C), was determined. *P<0.05, **P<0.01, ***P< 0.001.

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Capsaicinoids improve swallow in older patients with OD

Figure 3: Hyoid motion. Vertical (A) and anterior (B) hyoid movement during 5 mL swallows in older patients with dysphagia: Effect of thickener (A.1 and B.1) and capsaicinoids (A.2 and B.2) treatment on the hyoid motion profiles compared using two-way ANOVA analysis.

Figure 4: Maximal hyoid and larynx displacement times. Time of maximal vertical (A) and anterior (B) displacement of the hyoid bone (A.1 and B.1) and the larynx (A.2 and B.2) of older controls (black) and patients with dysphagia treated with thickener (white) and capsaicinoids (grey). *P< 0.05, **P< 0.01.

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Capítulo 5___________________________________________________________________

Discussion The main results of this study are that stimulation of oropharyngeal TRPV1 by natural capsaicinoids improved safety and efficacy of swallow and the physiology of swallow response in older patients with OD. We also found that the standard treatment for dysphagic patients, starch based thickener, improved safety of swallow without affecting the physiology of swallow response. Following our results, we believe stimulation of TRPV1 might become a new pharmacological strategy in patients with OD. The two main strategies used in the treatment of OD in the elderly are modification of food textures for solids and liquids and behavioural treatments with swallow postures, manoeuvres and exercises.[28,29] In previous studies, we found that enhancing bolus viscosity greatly increased safety of swallowing with a maximal therapeutic effect at pudding viscosity (3931.2 mPa s) in patients with neurogenic dysphagia and frail older patients.[3,23] The present study also confirms the strong therapeutic effect of thickeners on safety of swallow in older persons with OD. However, increasing bolus viscosity using starch thickeners increased oropharyngeal residue.[3,23,24] Otherwise, the level of evidence of the effect on the elderly of the classical rehabilitation and behavioural treatments with postures, manoeuvres and exercises is very weak and the variability in its application very high.[29] In addition, modified food textures or behavioural treatments are widely recognized to be compensatory strategies that do not change the impaired swallow physiology in patients with OD.[29] Our present study evaluates the possibility of treating swallowing disorders of patients with OD through a pharmacological approach involving the stimulation of oropharyngeal TRPV1.[30] To do this, we used a strategy of supplementation of the alimentary bolus with natural agonists of TRPV1. A capsaicinoid sauce was used as a source of natural TRPV1 agonist, because of its high content of capsaicinoids (185 µg/g), because it is a safe alimentary product, and because it has already been used in previous studies on humans showing its effectiveness in enhancing motility of the esophageal body in patients with esophageal

disorders.[22] We found that the swallow response was severely impaired in our elderly patients with OD with a serious delay in the early phase of oropharyngeal reconfiguration from a respiratory to a digestive pathway (time to LV closure and UES opening). These results, agree with an earlier study by Kahrilas[26] that found prolonged intervals to LV closure and UES opening are the key abnormalities of swallow response leading to unsafe deglutition (penetrations into laryngeal vestibule or aspiration into the airway) in neurological patients and also agree with our previous studies on frail elderly patients and neurological patients.[3,23] Time to LV closure is the time interval during which the potential penetration or aspiration occurs, and a delay in UES opening increases the risk for bolus overflow into the LV. Central or peripheral denervation[10] or direct brain stem damage might reduce the excitability of the central pattern generator and explain this serious delay in the initial reconfiguration phase of swallow response.[32] We found capsaicinoids had a strong therapeutic effect by enhancing the afferent sensorial input through stimulation of oropharyngeal TRPV1 channels, shortening LV closure and UES opening time and also, the time to maximal vertical extension of hyoid and larynx. Activation of suprahyoid muscles (geniohyoid, mylohyoid and anterior belly of the digastric), responsible for hyoid movement, is an early event in the swallow response following activation of the central pattern generator.[33] Hyoid motion drives laryngeal movement, LV closure and UES opening,[26,34] therefore the early occurrence of these events caused by capsaicinoids is in close association with the reduction of LV penetrations observed during capsaicinoid treatment. It is worth noting that capsaicinoids did not modify total duration of swallow response, their effects were concentrated in the first phase of swallow, that is the reconfiguration from a digestive pathway to a respiratory pathway. Animal studies showed that acetic and citric acids, which provide a sour taste, applied to the mucosa of the pharyngolaryngeal region had a similar strong facilitatory effect on swallow initiation caused by an increase in sensory inputs via the SLN and GPNph.[35] In addition, trigeminal nerve fibers also express several receptors that respond to chemicals including TRPV1 and acid sensing ion channels (ASIC).[36] These experimental findings are consistent with the

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Capsaicinoids improve swallow in older patients with OD independently living older persons. J Am Geriatr Soc 2011;59:186-187.

classical clinical observation that sour taste facilitates the onset of swallowing.[20,37] This effect of acid, exerted at least in part, through the TRPV1,[30,38] could contribute to the observed response, as pH of the supplemented bolus was more acidic than pH of the nectar control bolus. Other studies using TRPV1 agonists also show positive clinical results on the deglutition of patients with dysphagia.[14,17-19,21] For the first time, our study shows that this pharmacological strategy strongly and specifically improves the initial phase of the swallow response by speeding the interval to LV closure, to UES opening and to maximal vertical hyoid extention as well as stronger lingual propulsion. Our results agree with those of Pelleiter[39] who observed that high citric acid stimuli (0.128 M) led to higher peak lingual swallowing pressures than water. Desensitization was not observed in response to capsaicinoids in our clinical study. A study using 30-day treatment -6 with capsaicin (10 M/ three times at day) also found improvement in patients with OD.[18] The modification of the state of phosphorylation of TRPV1 by substance P and other neurotransmitters released by nerve afferents, might prevent their desensitization.[40] A possible limitation of the study is that, in order to minimize the exposition to the radiation of the patients, only one swallow per volume was tested in each patient, regardless of the possible within-subject variability. Further studies are needed to define the long-term effect of capsaicinoids on the impaired swallow response of chronic dysphagic patients and also to assess their effects in specific phenotypes of dysphagic patients. In summary, our study found that the swallow response could be improved by stimulation of oropharyngeal TRPV1 by natural capsaiciniods in older patients with OD, opening the door for pharmacological modulation and treatment of impaired swallow response and oropharyngeal dysphagia in older patients.

2. Clave P, Verdaguer A, Arreola V. [Oralpharyngeal dysphagia in the elderly]. Med Clin (Barc) 2005;124:742-748. 3. Rofes L, Arreola V, Romea M, et al. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010;22:851-8, e230. 4. Cabre M, Serra-Prat M, Palomera E, et al. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010;39:39-45. 5. Serra-Prat M, Palomera M, Gomez C, et al. Oropharyngeal dysphagia as a risk factor for malnutrition and lower respiratory tract infection in independently living older persons: a population-based prospective study. Age Aging 2012. 6. Aviv JE, Martin JH, Jones ME, et al. Agerelated changes in pharyngeal and supraglottic sensation. Ann Otol Rhinol Laryngol 1994;103:749-752. 7. Aviv JE. Effects of aging on sensitivity of the pharyngeal and supraglottic areas. Am J Med 1997;103:74S-76S. 8. Aviv JE, Martin JH, Sacco RL, et al. Supraglottic and pharyngeal sensory abnormalities in stroke patients with dysphagia. Ann Otol Rhinol Laryngol 1996;105:92-7. 9. Mortelliti AJ, Malmgren LT, Gacek RR. Ultrastructural changes with age in the human superior laryngeal nerve. Arch Otolaryngol Head Neck Surg 1990;116:1062-9. 10. Tiago R, Pontes P, do Brasil OC. Age-related changes in human laryngeal nerves. Otolaryngol Head Neck Surg 2007;136:747751. 11. Teismann IK, Steinstraeter O, Stoeckigt K, et al. Functional oropharyngeal sensory disruption interferes with the cortical control of swallowing. BMC Neurosci 2007;8:62.

References 1. Serra-Prat M, Hinojosa G, Lopez D, et al. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in

12. Hamdy S, Aziz Q, Rothwell JC, et al. Cranial nerve modulation of human cortical swallowing motor pathways. Am J Physiol 1997;272:G802-G808.

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Capítulo 5___________________________________________________________________ 13. Teismann IK, Steinstrater O, Warnecke T, et al. Tactile thermal oral stimulation increases the cortical representation of swallowing. BMC Neurosci 2009;10:71.

24. Clave P, Arreola V, Romea M, et al. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008;27:806-815.

14. Ebihara T, Ebihara S, Maruyama M, et al. A randomized trial of olfactory stimulation using black pepper oil in older people with swallowing dysfunction. J Am Geriatr Soc 2006;54:1401-1406.

25. Wallace KL, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of oral-pharyngeal dysphagia. Gastroenterology 2000;118:678-687.

15. Jean A. Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev 2001;81:929-969.

26. Kahrilas PJ, Lin S, Rademaker AW, et al. Impaired deglutitive airway protection: a videofluoroscopic analysis of severity and mechanism. Gastroenterology 1997;113:1457-1464.

16. Hamamoto T, Takumida M, Hirakawa A, et al. Localization of transient receptor potential vanilloid (TRPV) in the human larynx. Acta Otolaryngol 2009;129(5):560-568. 17. Ebihara T, Sekizawa K, Nakazawa H, et al. Capsaicin and swallowing reflex. Lancet 1993;341:432. 18. Ebihara T, Takahashi H, Ebihara S, et al. Capsaicin troche for swallowing dysfunction in older people. J Am Geriatr Soc 2005;53:824828. 19. Ebihara T, Ebihara S, Yamazaki M, et al. Intensive stepwise method for oral intake using a combination of transient receptor potential stimulation and olfactory stimulation inhibits the incidence of pneumonia in dysphagic older adults. J Am Geriatr Soc 2010;58:196-198. 20. Logemann JA, Pauloski BR, Colangelo L, et al. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995;38:556-563. 21. Watando A, Ebihara S, Ebihara T, et al. Effect of temperature on swallowing reflex in elderly patients with aspiration pneumonia. J Am Geriatr Soc 2004;52:2143-2144. 22. Gonzalez R, Dunkel R, Koletzko B, et al. Effect of capsaicin-containing red pepper sauce suspension on upper gastrointestinal motility in healthy volunteers. Dig Dis Sci 1998;43:1165-1171. 23. Clave P, de Kraa M, Arreola V, et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006;24:1385-1394.

27. Logemann JA, Rademaker AW, Pauloski BR, et al. A randomized study comparing the Shaker exercise with traditional therapy: a preliminary study. Dysphagia 2009; 24:403411. 28. Rofes L, Arreola V, Almirall J, et al. Diagnosis and Management of Oropharyngeal Dysphagia and Its Nutritional and Respiratory Complications in the Elderly. Gastroenterol Res Pract 2011;2011. . http://dx.doi.org/10.1155/2011/818979. Accessed June 12, 2012. 29. Speyer R, Baijens L, Heijnen M, et al. Effects of therapy in oropharyngeal dysphagia by speech and language therapists: a systematic review. Dysphagia 2010;25:40-65. 30. Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389:816-824. 31. Ursu D, Knopp K, Beattie RE, et al. Pungency of TRPV1 agonists is directly correlated with kinetics of receptor activation and lipophilicity. Eur J Pharmacol 2010;641:114-122. 32. Hamdy S, Aziz Q, Rothwell JC, et al. Explaining oropharyngeal dysphagia after unilateral hemispheric stroke. Lancet 1997;350:686-692. 33. Spiro J, Rendell JK, Gay T. Activation and coordination patterns of the suprahyoid muscles during swallowing. Laryngoscope 1994;104:1376-1382. 34. Leonard RJ, Kendall KA, McKenzie S, et al. Structural displacements in normal

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Capsaicinoids improve swallow in older patients with OD swallowing: a videofluoroscopic Dysphagia 2000;15:146-152.

study.

35. Kajii Y, Shingai T, Kitagawa J ,et al. Sour taste stimulation facilitates reflex swallowing from the pharynx and larynx in the rat. Physiol Behav 2002;77:321-325.

38. Tominaga M, Caterina MJ, Malmberg AB, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998;21:531-543. 39. Pelletier CA, Dhanaraj GE. The effect of taste and palatability on lingual swallowing pressure. Dysphagia 2006;21:121-128.

36. Bryant B, Silver WL. Chemesthesis: The common chemical sense. In: Finger TE, Silver WL, and Restrepo D, eds. Neurobiology of Taste and Smell. Wiley-Liss, Inc 2000:73-100. 37. Pelletier CA, Lawless HT. Effect of citric acid and citric acid-sucrose mixtures on swallowing in neurogenic oropharyngeal dysphagia. Dysphagia 2003;18:231-241.

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40. Sculptoreanu A, Aura KF, de Groat WC. Neurokinin 2 receptor-mediated activation of protein kinase C modulates capsaicin responses in DRG neurons from adult rats. Eur J Neurosci 2008;27:3171-3181.

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CAPÍTULO 6

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Oral piperine improves swallow response

Capítulo 6 EFFECT OF ORAL PIPERINE ON THE SWALLOW RESPONSE OF PATIENTS WITH OROPHARYNGEAL DYSPHAGIA Rofes L, Arreola V, Martin A, Clavé P. Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia. J Gastroenterol 2013; In press. doi:10.1007/s00535-013-0920-0

Abstract Background: Oropharyngeal dysphagia (OD) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients. In an earlier study, we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic patients. The aim of this study was to explore the effect of piperine, a dual TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients. Methods: A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine. Patients were randomized into two groups: one group received 150 µM piperine and the other one 1 mM. Results: Piperine improved the safety of swallow by: a) reducing the prevalence of unsafe swallows by 34.48% (P=0.004) at 150 µM and -57.19% (P<0.001) at 1 mM, and the severity score of the penetrationaspiration scale from 3.25±0.51 to 1.85±0.27 (P=0.003, 1mM), and b) shortening the time to laryngeal vestibule closure from 0.366±0.024s to 0.270±0.022s with 150 µM piperine (P<0.001) and from 0.380±0.032s to 0.306±0.028s with 1 mM (P<0.05). Conclusion: Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD, with a maximal therapeutic effect at 1mM. Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients.

Introduction Oropharyngeal dysphagia (OD) is a severe and prevalent gastrointestinal motility disorder specifically classified by the World Health Organization in the International Classification of Diseases, ICD-9 and ICD-10 [1]. It mostly affects older people (from 23% of independently-living elderly [2] to up to 51% of institutionalized elderly [3]), patients with a previous stroke (from 37% in the chronic phase to 78% in the acute phase) [4] and patients with neurodegenerative diseases (such as 82% of symptomatic patients with Parkinson’s disease [5] and more than 30% with multiple sclerosis [6]). OD in these patients is characterized by reduced safety of swallow with aspiration of food into the airways due to delayed laryngeal vestibule closure time and slow hyoid motion, and also by

high prevalence of oropharyngeal residue, due to weak bolus propulsion forces and impaired pharyngeal clearance [7,8]. Severe pharyngeal and laryngeal sensory deficits have also been described in post-stroke patients and elderly dysphagic patients [9,10]. OD causes clinically relevant complications such as malnutrition, dehydration and aspiration pneumonia, leading to prolonged institutionalization, decreased quality of life and high mortality rates [11]. However, therapeutic strategies for dysphagic patients are scarce, have a low level of evidence and tend to focus on compensating for the motor impairments instead of aiming to improve the swallow response [12].

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Capítulo 6___________________________________________________________________ We have recently found that the swallow physiology of patients with OD could be improved by administering natural capsaicinoids, which act at transient receptor potential cation channel, subfamily V, member 1 (TRPV1) [13]. Prevalence of pharyngeal residue and penetrations into the laryngeal vestibule were reduced with this treatment. These results gave rise to the pharmacological neuromodulatory treatment of impaired swallow response and OD through activation of TRP channels. Other clinical studies have shown that agonists of other TRP channels (such as piperine [14], acid [15,16], menthol [17] and temperature changes [18]) also modify swallow physiology. Piperine, the main component of Piper nigrum, activates both TRPV1 and the transient receptor potential channel, subfamily A, member 1 (TRPA1) [19]. Nasal inhalation of black pepper oil shortens the latency of swallow reflex, in both acute and chronic settings, and increases the regional cerebral blood flow in the right medial orbitofrontal cortex and the left insular cortex [14]. These promising preliminary results need further confirmation, as the specific effects of oral piperine on the physiology of swallow response and the appropriate dose to use remain unknown. The aim of our study was to examine the effect of oral piperine on the prevalence of videofluoroscopic signs of dysphagia and on the physiology of the swallow response of dysphagic patients in order to explore its potential value as a pharmacological therapeutic tool.

Material and Methods Study population A clinical study was carried out in the Gastrointestinal Physiology Laboratory and in the Radiology Unit of the Hospital de Mataró (Spain) between June 2011 and February 2012. We studied 40 patients (75.8±2.0 years, 17 men) with clinical signs of OD according to the Volume-Viscosity Swallow Test [20] associated with aging (>70 years) (n=23), neurodegenerative diseases (n=4) or stroke (n=13). Study protocol was approved by the Institutional Review Board of the Hospital de Mataró and was conducted according to the principles and rules laid down in the Declaration of Helsinki and its

subsequent amendments. Written informed consent was obtained from each of the included patients.

Study design This was a double-blind, interventional, controlled study, with a pre- post-treatment design, each patient acting as his/her own control. Patients were randomly assigned into two groups and received 1 mM or 150 µM piperine (Sigma-Aldrich, St Louis, MO, USA) corresponding to maximal and EC50 concentrations obtained in calcium imaging studies. Baseline characteristics were collected before the intervention: sociodemographic data, functional capacity according to the Barthel Index, comorbidities according to the Charlson Comorbidity Index and nutritional status according to the Mini Nutritional Assessment short form [21]. Clinical dysphagia symptoms were also obtained by means of the Eating Assessment Tool (EAT-10) [22] and the Sydney Swallow Questionnaire (SSQ) [23]. All participants were then imaged for the videofluoroscopic study, seated, in a lateral projection which included the oral cavity, pharynx, larynx, and cervical esophagus. Videofluoroscopic recordings were obtained with a Super XT-20 Toshiba Intensifier (Toshiba Medical Systems Europe, Zoetermeer, The Netherlands) and recorded at 25 frames/s using a Panasonic AG DVX-100B video camera (Matsushita Electric Industrial Co, Osaka, Japan). Patients were studied during the deglutition of one series of 5, 10 and 20 mL nectar control boluses (pH=6.35±0.03) and two series of 5, 10 and 20 mL nectar boluses supplemented with the corresponding concentration of piperine: 150 µM, pH=6.49±0.08 and 1 mM, pH=6.57±0.03. Following the nectar control series, a sensitization process was conducted on each patient by administering two 5-mL boluses, also supplemented with the corresponding concentration of piperine (1mM or 150 µM depending on the group), 5 min before the first treatment bolus series, and then the two piperine-supplemented bolus series were administered 10 min apart. Nectar viscosity (274.42±13.14 mPa s) was obtained by adding 3.5 g of thickener Resource ThickenUp (Nestlé Nutrition, Barcelona, Spain) to 100 mL of liquid made 1:1 with mineral water and the X-ray contrast Gastrografin (Bayer Hispania SL, Sant Joan Despí, Spain). Boluses were carefully offered to patients with a syringe.

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Data analysis Videofluoroscopic signs. Videofluoroscopic signs of safety and efficacy of deglutition were identified accordingly to previously accepted definitions: impaired tongue propulsion, oral residue and inefficient glossopalatal seal were assessed in the oral phase; vallecular, pyriform sinus residue, laryngeal vestibule penetrations and aspirations (classified according to the Penetration-Aspiration Scale [24]), and upper esophageal sphincter opening were assessed in the pharyngeal phase [7,8]. Oropharyngeal swallow response. Digitization, analysis and measurements of videofluoroscopic images were made using the software Swallowing Observer (Image and Physiology SL, Barcelona, Spain). The following quantitative measurements of oropharyngeal swallow response were obtained during 5 mL swallows: a) Oropharyngeal reconfiguration - timing of the opening and closing of the glossopalatal junction (GPJ), velopharyngeal junction (VPJ), laryngeal vestibule (LV), and upper esophageal sphincter (UES), GPJ opening being given the time value 0; b) Hyoid motion - vertical and anterior hyoid position was determined in an xy coordinate system in each frame. The anteriorinferior corner of C3 was used as the origin and the vertical axis was defined by a line connecting the anterior inferior corners of C3 and C5, and c) Bolus -1 kinematics – mean bolus velocity (m s ) from the GPJ to the UES was also calculated.

Adverse events Adverse events occurring during the study were documented and possible relationship to the study procedures assessed according to the Karch and Lasagna algorithm.

Statistical methods Categorical variables were described as relative and absolute frequencies and compared by the Fisher’s exact test (comparisons between groups) or the McNemar’s test (comparisons within each group). Quantitative parameters were described by mean±SEM. Comparisons between groups were assessed by the non-parametric Mann–Whitney U-

Test and comparisons within each group were assessed by the non-parametric Wilcoxon matched pairs test. Statistical significance was accepted if P values were less than 0.05. Statistical analysis was performed using GraphPad Prism 5.01 (San Diego, CA, USA).

Results Baseline characteristics Demographic and clinical characteristics of the study population are summarized in Table 1. Patients included in the study presented advanced age (75.8±2.0 years), multimorbidity (Charlson Comorbidity Index 2.7±0.3), impaired functional capacity (Barthel Index 76.1±5.2), high risk of malnutrition (Mini Nutritional Assessment short form, MNA-SF 10.5±0.5), and clinical complaints of OD (EAT-10 and SSQ questionnaires). According to the V-VST, 62.5% of patients presented signs of both impaired safety and efficacy of swallow, 7.5% only in safety and 30.0% only in efficacy.

Effect of piperine on videofluoroscopic signs of impaired safety and efficacy of swallow All patients included in the study presented severe impairment in swallow physiology characterized by high prevalence of videofluoroscopic signs of impaired safety (70%) and/or efficacy (45%) of swallow, summarized in Figure 1. There were no significant differences between groups in the prevalence of videofluoroscopic signs of impaired safety or efficacy of swallow at nectar control viscosity. Treatment with piperine reduced the prevalence of penetrations by -34.48% (P=0.004) at 150 µM and -57.19% (P<0.001) at 1 mM (Figure 1). Maximum score on the Penetration-Aspiration Scale was not significantly affected by the treatment with 150 µM of piperine (2.10±0.25 control bolus and 1.95±0.36 150 µM piperine supplemented bolus, P=0.521) but was significantly reduced in the group of patients treated with 1 mM piperine (3.25±0.51 nectar control bolus to 1.85±0.27 1 mM piperine supplemented bolus, P=0.003). Prevalence of oral and pharyngeal residues were not significantly affected by piperine (Figure 1).

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Capítulo 6___________________________________________________________________ Table1. Demographic, clinical and nutritional characteristics of the study population. MNA-SF, Mini Nutritional Assessment short form; EAT-10, eating assessment tool -10; SSQ, Sydney Swallow Questionnaire.

75.8±2.0 17 (42.5%)

150 µM group (n=20) 76.6±2.4 9 (45%)

1 mM group (n= 20) 75.05±3.3 8 (40%)

23 (60.5%)

11 (55.0%)

12 (60.0%)

13 (32.5%)

5 (25%)

8 (40%)

4 (10.0%)

4 (20.0%)

0 (0.0 %)

76.1±5.2 2.7±0.3

78.0±6.9 2.6±0.3

74.2±7.9 2.9±0.5

0.668 0.701

17 (47.2%)

10 (52.6%)

7 (41.2%)

0.638

12 (33.3%)

5 (26.3%)

7 (41.2%)

7 (20.6%) 11.8±1.3 529.6±44.9

4 (21.0%) 11.5±1.8 541.0±69.2

3 (17.7%) 12.1±1.9 518.1±59.1

All (N=40) Age (years) Sex (men) Associated pathologies: Aging (>70 years) Non-progressive neurological disease Neurodegenerative disease Barthel Index Charlson Index MNA-SF: Normal nutritional status (12-14) At risk of malnutrition (8-11) Malnourished (0-7) EAT-10 SSQ

P value 0.797 1.00

0.094

0.957 0.787

Figure 1. Effect of piperine on videofluoroscopic signs of impaired safety and efficacy of swallow Effect of piperine 150 µM (black circles) and 1 mM (white circles) on the prevalence of laryngeal vestibule penetrations (left), oral residue (middle) and pharyngeal residue (right). *p<0.05, **p<0.01

Effect of piperine on the physiology of impaired swallow response a) Oropharyngeal reconfiguration. Bolus supplementation with piperine greatly shortened time to LV closure: 150 µM piperine reduced closure time from 0.366±0.024 s to 0.270±0.022 s

(-26.2%, P<0.001) and 1 mM piperine from 0.380±0.032 s to 0.306±0.028 s (-19.5%, P<0.05). In contrast, UES opening time was not affected by piperine at either concentration. Total duration of swallow response (GPJ opening-to LV opening time) was shortened in the first series of boluses

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Oral piperine improves swallow response

supplemented with 150 µM piperine (1.00±0.045 s at control bolus vs 0.896±0.039 s at 150 µM piperine supplemented boluses, -10.4%, P<0.01) but not during the administration of 1 mM piperine concentration (1.03±0.051 s at control bolus vs 0.972±0.071 s at 1 mM piperine supplemented boluses, P>0.05) (Figure 2). When the population was divided according to patient phenotype we found that, in older patients, bolus supplementation with piperine shortened the LV closure time from

0.363±0.023 s to 0.294±0.027 s (-19.0%, P<0.01) and, in patients with stroke, from 0.372±0.043 s to 0.255±0.019 s (-31.5%, P<0.01) b) Hyoid motion. Maximal vertical (20.11±1.56 mm) and anterior (41.68±1.34 mm) extensions were not affected by piperine at either of the concentrations tested; nor was the maximal vertical extension time (0.484±0.031 s). In contrast, the time needed to reach the maximum anterior extension of the hyoid was shortened by both concentrations of piperine, 150 µM piperine (0.668±0.058 s at nectar control bolus vs 0.514±0.038 s at bolus with 150 µM piperine, P<0.05), and 1 mM piperine (0.728±0.064 s at nectar control bolus vs 0.571±0.047 s at bolus with 1 mM piperine, P<0.05). c) Bolus kinematics. Mean bolus velocity was not affected significantly by the supplementation of the alimentary bolus with piperine at either of the two tested concentrations (from 0.209±0.018 m/s to 0.238±0.018 m/s, P=0.066, at 150 µM and from 0.196±0.019 m/s to 0.217±0.018 m/s, P=0.320, at 1 mM).

Adverse events One adverse event (abdominal pain) was registered in the 1 mM piperine group, but it was not considered serious nor related to the study product.

Figure 2. Effect of piperine on the timing of oropharyngeal reconfiguration Timing of main events of the oropharyngeal swallow response during 5 mL swallows. Effect of piperine 150 µM (light grey bars) and 1 mM (dark grey bars) on the laryngeal vestibule closure time (top), upper esophageal sphincter opening time (middle) and laryngeal vestibule opening time (bottom), was determined. **p<0.01, ***p<0.001.

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Capítulo 6___________________________________________________________________

Discussion This study shows that the dual TRPV1/TRPA1 agonist piperine specifically and significantly improved safety of swallow of patients with dysphagia by speeding the time to airway closure, leading to a reduction in the prevalence and the severity of penetrations and aspirations. Our results suggest that impaired swallow response can be treated pharmacologically. Standard treatment of OD consists of compensatory therapies, such as increasing liquid viscosity with thickeners, modifying texture of solids and adopting postural strategies, and rehabilitation therapies that aim to improve the swallow function through maneuvers and motor exercises. Compensatory strategies improve the safety of swallow but do not modify swallow biomechanics and do not promote swallow recovery and current rehabilitation strategies require a better cognitive level than many dysphagic patients present. Moreover, despite their widespread use, the level of evidence of these behavioral therapies is low [12]. In recent years, a new set of therapies based on neurostimulation have emerged. They aim to restore impaired swallow physiology by stimulating neural plasticity [25]. They can be classified into those that directly stimulate the pharyngeal motor cortex and corticobulbar pathways, the non-invasive brain stimulation techniques, and those that enhance the oropharyngeal afferent input by means of physical [26], electrical [27,28] or chemical [13] stimuli. The non-invasive brain stimulation techniques include repetitive transcranial magnetic stimulation (rTMS) [29] and transcranial direct current stimulation (tDCS) [30], both of which showed promising results in the first studies performed, but are limited by needing specific (and expensive in the case of rTMS) equipment and welltrained professionals to manage them. In addition, application seems limited to specific etiologies of dysphagia such as post-stroke patients. On the other hand, the neurostimulation techniques applied to the somatosensory system aim to induce reorganization of neural connections by applying peripheral stimulus in the oropharynx. Piperine is a sensory chemical stimulant that activates the TRPV1 and TRPA1 channels expressed in the sensory neurons of the oropharynx, such as the

maxillary branch of trigeminal nerve (V cranial nerve), the pharyngeal branch of the glossopharyngeal nerve (GPNph, IX cranial nerve) and two branches of the vagus nerve (X cranial nerve), the pharyngeal branch (Xph) and the superior laryngeal nerve (SLN) [31] and increases the sensory input to the brainstem and to the cortex, facilitating the triggering of the swallow response and potentially promoting neuronal reorganization. In addition, piperine could also act retronasally, activating the TRP channels expressed in olfactory sensory neurons [32] and enhancing the activation of the cortex [14]. Supplementing the alimentary bolus with piperine or other TRP agonists is an easy and cheap strategy that does not require patient collaboration, specific equipment or trained staff. Patients included in the present study presented oropharyngeal dysphagia associated to aging, neurodegenerative diseases or stroke. This is an important point as most of the new neuromodulation techniques focus on post-stroke dysphagic patients and their effect on other dysphagia etiologies has not been investigated. The vulnerability of our population is apparent in their advanced age, multimorbidity, and poor functional and nutritional status and solutions that minimize the risk of further complications are necessary, the treatment of dysphagia being a priority. In our study, piperine reduced the prevalence of penetrations into the laryngeal vestibule at both concentrations and the severity of the penetrations at the highest concentration. Protecting patients from penetrations and aspirations is the main aim of dysphagia therapy as it has been extensively reported that impaired safety of swallow is a poor prognostic factor related with aspiration pneumonia and high mortality rates in frail elderly people [8], in elderly patients with pneumonia [33,34], in post-stroke [4,35,36] and in elderly hospitalized patients [37]. Hitherto, modification of bolus properties (viscosity and density) has been used to improve swallow safety by adapting boluses to impaired swallow physiology. This study shows that piperine protected the airways without any modification in the rheological properties of the bolus but by changing the swallow physiology, specifically by accelerating the laryngeal vestibule closure time. This effect was reported in a previous study using natural capsaicinoids at acidic pH [13]. However,

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Oral piperine improves swallow response

questions were raised over whether the acidic pH used in that study was partly responsible for the TRP stimulation and the observed therapeutic effect. In this study, the pH of the supplemented bolus and the control bolus was similar, so the observed effect can only be attributable to piperine. Piperine is a dual TRPV1/A1 agonist, although it activates TRPV1 more strongly than TRPA1 [19]. This could mean that the contribution of TRPV1 in the observed effects is higher than TRPA1. In order to determine the specific contribution of TRPA1, a further study using a selective TRPA1 agonist, such as cinnamaldehyde, should be performed. Likewise, unspecific TRP-independent effects cannot be completely ruled out in our study as we did not use TRP antagonists. In contrast to the study with capsaicinoids, when we supplemented the bolus with piperine no effects were observed in terms of oropharyngeal residue or bolus kinematics, indicating that we obtained a pure neurological effect without changing muscle performance. Unfortunately, no neuroimages or neurophysiologic studies could be performed to confirm the effects of oral piperine at the neurological level but a previous study evaluating the effect of nasal inhalation of piperine reported greater activation of the anterior cingulate cortex and the left insular cortex after treatment with this stimulant [14]. Further studies should be performed to measure the long-term effects of the therapy, as well as the effects on specific phenotypes of dysphagic patients. In summary, supplementing the alimentary bolus with piperine improves swallow response in dysphagic patients. The study confirms that the activation of the TRPV1/A1 of sensory neurons is a valid strategy that could be used to develop a pharmacological treatment for these patients.

References 1. World Health Organization. ICD-10 Version:2010 [online]. 2010 [cited 29 April 2013]. Available from: http://apps.who.int/classifications/icd10/browse/ 2010/en#/R13 2. Serra-Prat M, Hinojosa G, Lopez D, et al. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in

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independently living older persons. J Am Geriatr Soc 2011; 59: 186-7. 3. Lin LC, Wu SC, Chen HS, Wang TG, Chen MY. Prevalence of impaired swallowing in institutionalized older people in Taiwan. J Am Geriatr Soc 2002; 50: 1118-23. 4. Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005; 36: 2756-63. 5. Kalf JG, de Swart BJM, Bloem BR, Munneke M. Prevalence of oropharyngeal dysphagia in Parkinson's disease: A meta-analysis. Parkinsonism & Related Disorders 2012; 18: 311-15. 6. Prosiegel M, Schelling A, Wagner-Sonntag E. Dysphagia and multiple sclerosis. Int MS J 2004; 11: 22-31. 7. Clave P, de Kraa M, Arreola V, et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006; 24: 1385-94. 8. Rofes L, Arreola V, Romea M, et al. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010; 22: 851-8, e230. 9. Aviv JE, Martin JH, Jones ME, et al. Agerelated changes in pharyngeal and supraglottic sensation. Ann Otol Rhinol Laryngol 1994; 103: 749-52. 10. Aviv JE, Martin JH, Sacco RL, et al. Supraglottic and pharyngeal sensory abnormalities in stroke patients with dysphagia. Ann Otol Rhinol Laryngol 1996; 105: 92-7. 11. Rofes L, Arreola V, Almirall J, et al. Diagnosis and management of oropharyngeal dysphagia and its nutritional and respiratory complications in the elderly. Gastroenterol Res Pract [online journal]. 2011 [cited 29 April 2013]; 2011: [about 13 pages]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2 929516/ 12. Speyer R, Baijens L, Heijnen M, Zwijnenberg I. Effects of therapy in oropharyngeal dysphagia by speech and language therapists: a systematic review. Dysphagia 2010; 25: 40-65.

Capítulo 6___________________________________________________________________ 13. Rofes L, Arreola V, Martin A, Clavé P. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia. Gut 2013; 62: 1280-7.

oral-pharyngeal dysphagia. Gastroenterology 2000; 118: 678-87. 24. Rosenbek J, Robbins J, Roecker E. A penetration-aspiration scale. Dysphagia 1996; 11: 93-8.

14. Ebihara T, Ebihara S, Maruyama M, et al. A randomized trial of olfactory stimulation using black pepper oil in older people with swallowing dysfunction. J Am Geriatr Soc 2006; 54: 140106.

25. Rofes L, Vilardell N, Clave P. Post-stroke dysphagia: Progress at last. Neurogastroenterol Motil 2013; 25: 278-82.

15. Hamdy S, Jilani S, Price V, Parker C, Hall N, Power M. Modulation of human swallowing behaviour by thermal and chemical stimulation in health and after brain injury. Neurogastroenterol Motil 2003; 15: 69-77.

26. Teismann IK, Steinstrater O, Warnecke T, et al. Tactile thermal oral stimulation

16. Logemann JA, Pauloski BR, Colangelo L, Lazarus C, Fujiu M, Kahrilas PJ. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995; 38: 55663.

27. Gallas S, Marie JP, Leroi AM, Verin E. Sensory transcutaneous electrical stimulation improves post-stroke dysphagic patients. Dysphagia 2010; 25: 291-7.

increases the cortical representation swallowing. BMC Neurosci 2009; 10: 71.

28.

17. Ebihara T, Ebihara S, Watando A, et al. Effects of menthol on the triggering of the swallowing reflex in elderly patients with dysphagia. Br J Clin Pharmacol 2006; 62: 369-71. 18. Watando A, Ebihara S, Ebihara T, et al. Effect of temperature on swallowing reflex in elderly patients with aspiration pneumonia. J Am Geriatr Soc 2004; 52: 2143-4.

30. Kumar S, Wagner CW, Frayne C, et al. Noninvasive Brain Stimulation May Improve Stroke-Related Dysphagia: A Pilot Study. Stroke 2011; 42: 1035-40. 31.

Jean A. Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev. 2001; 81: 929-69.

32. Nakashimo Y, Takumida M, Fukuiri T, Anniko M, Hirakawa K. Expression of transient receptor potential channel vanilloid (TRPV) 1– 4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazoletreated mouse olfactory epithelium. Acta Otolaryngol. 2010;130:1278-86.

21. Vellas B, Guigoz Y, Garry PJ, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition 1999; 15: 116-22. 22. Belafsky PC, Mouadeb DA, Rees CJ, et al. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol 2008; 117: 919-24.

Jayasekeran V, Singh S, Tyrrell P, et al. Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions. Gastroenterology 2010; 138: 1737-46.

29. Park JW, Oh JC, Lee JW, Yeo JS, Ryu KH. The effect of 5Hz high-frequency rTMS over contralesional pharyngeal motor cortex in poststroke oropharyngeal dysphagia: a randomized controlled study. Neurogastroenterol Motil 2013; 25: 324-e250.

19. Okumura Y, Narukawa M, Iwasaki Y, et al. Activation of TRPV1 and TRPA1 by Black Pepper Components. Biosci Biotechnol Biochem 2010; 74: 1068-72. 20. Clave P, Arreola V, Romea M, Medina L, Palomera E, Serra-Prat M. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008; 27: 806-15.

of

33.

23. Wallace KL, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of

- 118 -

Almirall J, Rofes L, Serra-Prat M, et al. Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly. Eur Respir J 2013; 41: 923-8.

Oral piperine improves swallow response 34. Cabre M, Serra-Prat M, Palomera E, Almirall J, Pallares R, Clave P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010; 39: 39-45. 35. Katzan IL, Cebul RD, Husak SH, Dawson NV, Baker DW. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003; 60: 620-5. 36. Hilker R, Poetter C, Findeisen N, et al. Nosocomial pneumonia after acute stroke: implications for neurological intensive care medicine. Stroke 2003; 34: 975-81. 37. Altman KW, Yu GP, Schaefer SD. Consequence of dysphagia in the hospitalized patient: impact on prognosis and hospital resources. Arch Otolaryngol Head Neck Surg 2010; 136: 784-9.

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CAPÍTULO 7

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Motor vs sensory electrical stimulation in dysphagia

Capítulo 7 EFFECT OF SURFACE SENSORY AND MOTOR ELECTRICAL STIMULATION ON CHRONIC POST -STROKE OROPHARYNGEAL DYSFUNCTION Rofes L, Arreola V, López I, Martin A, Sebastián M, Ciurana A, Clavé P. Effect of surface sensory and motor electrical stimulation on chronic poststroke oropharyngeal dysfunction. Neurogastroenterol Motil 2013; 25(11):888-e701

Abstract Background: Chronic post-stroke oropharyngeal dysfunction (OD) is a common condition, leading to severe complications, including death. Treatments for chronic post-stroke OD are scarce. The aim of our study was to assess and compare the efficacy and safety of treatment with surface electrical stimulation at sensory and motor intensities in patients with chronic post-stroke OD. Methods: Twenty chronic post-stroke patients with OD were randomly assigned to: a) sensory electrical stimulation (treatment intensity: 75% of motor threshold) or b) motor electrical stimulation (treatment intensity: motor threshold). Patients were treated during 10 days, 1 hour per day. Videofluoroscopy was performed at the beginning and end of the study to assess signs of impaired efficacy and safety of swallow and timing of swallow response. Results: Patients presented advanced age (74.95±2.18), 75% were men. The mean days post-stroke was 336.26±89.6. After sensory stimulation, the number of unsafe swallows was reduced by 66.7% (P<0.001), the laryngeal vestibule closure time by 22.94% (P=0.027) and maximal vertical hyoid extension time by 18.6% (P=0.036). After motor stimulation, the number of unsafe swallows was reduced by 62.5% (P=0.002), the laryngeal vestibule closure time by 38.26% (P=0.009) and maximal vertical hyoid extension time by 24.8% (P=0.008). Moreover, the motor stimulus reduced the pharyngeal residue by 66.7%, (P=0.002), the upper esophageal sphincter opening time by 39.39% (P=0.009) and increased bolus propulsion force by 211.1% (P=0.008). No serious adverse events were detected during the treatment. Conclusion: Surface electrical stimulation is a safe and effective treatment for chronic post-stroke dysphagic patients.

Introduction Oropharyngeal dysfunction (OD) is a common condition after stroke, present in up to 78% of acute stroke patients [1]. The swallowing function recovers spontaneously in about 50% of patients the first weeks after stroke, but chronically persist in the other half of patients and severe complications frequently arise [2]. OD can produce two types of complications in stroke patients [3]: malnutrition and/or dehydration caused by alterations in the efficacy of deglutition, and aspiration pneumonia (AP) caused by impairment in the safety of swallow. AP is one of the major causes of mortality in stroke patients the first year after discharge [4].

The standard of care for the majority of patients with stroke suffering from OD is very poor as 80% of them are not even diagnosed and do not receive any treatment for this condition [5]. For many years, dysphagia therapy for stroke patients has been focused on behavioral compensatory strategies including changes in viscosity of fluids with thickeners, modifying texture of solid food as well as postures and maneuvers [6]. These behavioral strategies have been proved to improve safety of swallow but not the impaired swallow biomechanics [3] and do not lead to recovery of damaged neural swallow networks. The surface electrical stimulation (e-stim) with the application of external electrical stimulation to the

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Capítulo 7___________________________________________________________________ muscles necessary for pharyngeal contraction was approved by the FDA in 2002 for dysphagia treatment. The first study to examine its effects on post-stroke dysphagic patients reported a significant improvement which lasted two years after treatment [7]. Since then, however, several studies have explored the safety and efficacy of e-stim, most of them reporting positive results, but many have been criticized for poor methodological quality [8;9]. Additionally, in recent years, two groups of treatments focusing on cortical neuroplasticity to recover swallowing function have been developed: those applied to the central nervous system (such as repetitive transcranial magnetic stimulation (rTMS) [10;11] or transcranial direct current stimulation (tDCS) [12] and those applied to the periphery (such as intra-pharyngeal electrical stimulation [13], tactile-thermal stimulation [14] and chemical stimulation [15]). Even though these new strategies (like rTMS and tDCS) have demonstrated their positive effects on swallow function recovery, they are still under investigation and most are not available for clinical practice. Recent studies suggest that the integration of the surface electrical stimulus by the oropharyngeal sensory neurons might also induce neuroplastic changes that could be, in part, responsible for swallowing recovery, and propose the application of surface e-stim at the sensory threshold [16]. As the number of well designed studies are limited, the optimal stimulation parameters have not been established, nor the effects of the therapy on the swallow physiology nor the mechanisms of action of the therapy. Much more research has been recommended to determine whether surface electrical stimulation has a role to play in the management of post-stroke oropharyngeal swallowing disorders [17;18]. The aim of this study was to assess and compare the efficacy and safety of 10 days of treatment with surface electrical stimulation at sensory and motor intensities, on chronic post-stroke patients with OD.

Material and Methods Patients Patients over the age of 18, with a previous stroke (over 3 months prior), clinical complaints of OD on discharge and who signed the informed consent,

were screened for eligibility in the study, from January 2012 to October 2012, in the Gastrointestinal Physiology Laboratory of the Hospital de Mataró (Spain). Study protocol was approved by the Institutional Review Board of the Hospital de Mataró and was conducted according to the principles and rules laid down in the Declaration of Helsinki and its subsequent amendments. Trial registration: NCT01363973.

Study design This was a proof of concept study to evaluate and compare the safety and efficacy of surface e-stim applied at sensory and motor intensities on patients with chronic post-stroke OD. A randomized, doubleblind, parallel group study was designed where each patient acted as his or her own control. A initial visit was performed before the intervention and sociodemographic data, functional capacity according to the Barthel Index, co-morbidities according to the Charlson Comorbidity Index and nutritional status according to the Mini Nutritional Assessment short form [19] were collected. Clinical dysphagia symptoms were obtained by means of the Eating Assessment Tool (EAT-10) [20] and the Sydney Swallow Questionnaire (SSQ) [21]. A videofluoroscopic study was performed on all participants. Patients who presented a score of 3 or higher on the Penetration–Aspiration scale (PAS) [22] were randomized to receive 10 days of surface e-stim treatment in one of two procedures: sensory electrical stimulation (treatment intensity, 75% of motor threshold; electrode placement, thyro-hyoid) or motor electrical stimulation (treatment intensity, motor threshold; electrode placement, supra-hyoid). Both the sensory and the motor threshold were determined three times before each session. Treatment consisted of the application, at rest, of 80 Hz of transcutaneous electrical stimulus (biphasic, 700 µs) using the Intelect VitalStim device (Chattanooga Group, Hixson, TN, USA), 1 hour per day. The VitalStim device is the only e-stim device approved by the FDA for dysphagia treatment. Sessions were applied from Monday to Friday for two weeks. Five days after the last treatment session, patients were re-evaluated by videofluoroscopy and swallowing questionnaires.

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Motor vs sensory electrical stimulation in dysphagia

Videofluoroscopic procedures Patients were imaged while seated, in a lateral projection which included the oral cavity, pharynx, larynx, and cervical esophagus. Videofluoroscopic recordings were obtained by a Super XT-20 Toshiba Intensifier (Toshiba Medical Systems Europe, Zoetermeer, The Netherlands) and recorded at 25 frames/s using a Panasonic AG DVX-100B video camera (Matsushita Electric Industrial Co, Osaka, Japan). Patients were studied during the deglutition of one series of nectar boluses (274.42±13.14 mPa s), one series of liquid boluses (20.40±0.23 mPa s) and one series of pudding boluses (3931.23±166.15 mPa s). Nectar viscosity was obtained by adding 3.5 g and pudding by adding 8 g of thickener Resource ThickenUp (Nestlé Nutrition, Barcelona, Spain) to 100 mL of liquid made with 1:1 mineral water and the X-ray contrast Gastrografin (Bayer Hispania SL, Sant Joan Despí, Spain). Boluses were carefully offered to patients with a syringe.

Efficacy measurements Swallowing questionnaires. The Eating Assessment Tool (EAT-10) and the Sydney Swallow Questionnaire (SSQ) were administered to all patients before and after the treatment [23]. The EAT-10 is a 10-item screening questionnaire consisting of 10 questions with answers graded 0-4 (0=no problem, 4=severe problem) on the symptoms, and clinical and social impact of oropharyngeal dysphagia. The SSQ is a 17-item clinical inventory designed to evaluate physiological aspects of oral and pharyngeal swallowing functions and establish the severity of oropharyngeal dysphagia. Each question is answered on a 100 mm visual analogue scale. Videofluoroscopic findings. Signs of safety and efficacy of deglutition were identified accordingly to previously accepted definitions [3;24]. Efficacy signs: presence of oral, vallecular and pyriform sinus residue was assessed in each deglutition. Safety signs: laryngeal vestibule penetrations and tracheobronquial aspirations, classified according to the PAS, were assessed in each deglutition. A score of 3 or higher in the PAS was considered an unsafe swallow.

Oropharyngeal swallow response. To assess the rearrangement of the oropharyngeal structures from a respiratory pathway to a digestive pathway and the return to the respiratory pathway when the deglutition is finished, the videofluoroscopic images were digitized and analyzed using the software Swallowing Observer (Image and Physiology SL, Barcelona, Spain). Quantitative measurements of oropharyngeal swallow response were obtained during 5 mL swallows. a) Temporal analysis of swallow: timing of the opening and closing of the glossopalatal junction (GPJ), velopharyngeal junction (VPJ), laryngeal vestibule (LV), and upper esophageal sphincter (UES) were measured, GPJ opening was given the time value 0, being considered the beginning of the pharyngeal phase of swallow; b) Hyoid motion: vertical and anterior hyoid position was determined in an xy coordinate system in each frame, the anterior-inferior corner of C3 was used as the origin and the vertical axis was defined by a line connecting the anterior-inferior corners of C3 and C5; c) Bolus kinematics: mean bolus velocity (m/s) was calculated measuring the distance between the GPJ and the UES and calculating the time that the bolus spent from the GPJ to the UES, and bolus propulsion force (mN) was measured by means of Newton’s second law of motion [24].

Adverse events Any adverse events occurring during the study were documented and assessed for relationship to the study procedures.

Statistical analysis Qualitative data are described as absolute and relative frequencies and compared by the Fischer’s exact test (for comparison between groups) and McNemar’s test (for evaluation before-after treatment). Quantitative data are described by the mean±SEM and compared by the U Mann-Whitney test (for comparisons between groups) or the Wilcoxon signed rank test (for comparisons beforeafter treatment). Statistical significance was accepted if P values were less than 0.05. Statistical analysis was performed using GraphPad Prism 5.01 (San Diego, CA, USA).

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Capítulo 7___________________________________________________________________

Results Patient characteristics A total of 42 patients were screened for eligibility in the study. Of these, 22 patients dropped out of the study before the treatment because they presented safe swallow in the VFS (PAS<3), were not able to follow the protocol or wished to withdraw. The remaining 20 were randomized, 10 to the sensory group and 10 to the motor group. All the randomized patients completed the treatment (Figure 1). Patients included in the study presented advanced age (74.95±2.18) and 75% (15] were men. The mean days post-stroke was 336.26±89.6, the etiology of the stroke was mainly ischemic (84.2%) and 63.2% were left-sided. Both treatment groups had comparable data at baseline (Table 1).

Figure 1. Trial flow chart.

Table 1. Demographic, clinical and nutritional characteristics of the study population. MNA-SF, Mini Nutritional Assessment short form; EAT-10, eating assessment tool -10; SSQ, Sydeny Swallow Questionnaire.

Sensory group 1

Motor group 2

P value

(n=10)

(n=10)

Age (years)

72.2 ±3.6

77.7 ±2.3

0.363

Sex (men)

7 (70.0%)

8 (80.0%)

1.00

228.3±48.3

433.4±162.6

0.438

Ischemic

9 (90%)

8 (80.0%)

1.00

Hemorrhagic

1 (10 %)

2 (20.0%)

Left

8 (80 %)

6 (60.0%)

Right

1 (10%)

2 (20.0%)

Brainstem

1 (10%)

2 (20.0%)

Charslon co-morbidity index

4.1±0.48

2.8±0.36

0.078

Barthel functionality index

81.5±7.8

82.5±7.5

0.725

Well nourished

1 (10%)

1 (10%)

1.00

At risk of malnutrition

4 (40%)

4 (40%)

Malnourished

5 (50%)

5 (50%)

EAT-10

8.3±2.8

4.9±0.6

0.349

EAT-10 <3

3 (30%)

2 (20%)

1.00

312.1±81.1

317.4±21.2

0.660

Stroke characteristics: Days from episode Etiology

Laterality 0.707

Nutritional status (MNA-SF)

Swallowing questionnaires

SSQ

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Motor vs sensory electrical stimulation in dysphagia

Effect of treatments Swallowing questionnaires. The basal scores of the symptom questionnaires EAT-10 and SSQ are included in Table 1 and are similar between both groups. After the treatment, patients in both groups reported improved oropharyngeal dysphagia symptoms. Patients allocated to the motor group presented significant improvement in the SSQ (31.4%, P=0.028) but not in the EAT-10 (-26.5%, P>0.05). However, the decrease in the questionnaire score was not statistically significant in the group that received the sensory stimulus (26.5% in the EAT-10 and -20.1% in the SSQ, P>0.05). Videofluoroscopic signs. Before the treatment, prevalence of unsafe swallows and oropharyngeal residue were 29.8% and 43.3% respectively. Maximum PAS score in the VFS screening was 3 in

35% of patients, 4 in 35%, 5 in 15%, 7 in 5% and 8 in 10%. Safety of swallow was significantly improved by both treatment intensities. The sensory stimulus reduced the number of unsafe swallows by 66.7% (P<0.001) and the motor stimulus had a similar effect, reducing unsafe swallows by 62.5% (P=0.002) (Figure 2A). However, the mean PAS score was only reduced in the group of patients that were treated with the sensory stimulus (from 5.0 to 2.7, P=0.009), not the motor group (from 3.6 to 3.3, P=0.521). Regarding efficacy of swallow, oral residue was significantly reduced by both treatment intensities: the sensory stimulus reduced the prevalence of oral residue by 66.2% (P=0.011) and the motor stimulus by 70.7% (P=0.002). Pharyngeal residue was only significantly reduced by the motor treatment (66.7%, P=0.002), not in patients treated with sensory intensities (20.7%, P=0.211) (Figure 2B).

Figure 2. Videofluoroscopic signs. A) Prevalence of unsafe swallows before (white bars) and after (grey bars) the treatment with surface electrical stimulation at sensory (left) and motor (right) intensities. B) Prevalence of pharyngeal residue before (white bars) and after (grey bars) the treatment with surface electrical stimulation at sensory (left) and motor (right) intensities. Prevalence is expressed as the number of swallows that presented the sign during the videofluoroscopic study versus total number of swallows performed. **P<0.01; ***P<0.001.

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Capítulo 7___________________________________________________________________ Oropharyngeal swallow response. Temporal analysis of swallow: Patients included in the study presented a prolonged and delayed swallow response. The LV closed at 448±31 ms, opened at 1080±45 ms and the UES opened at 396±34 ms. The LV closure and opening times were significantly reduced by both treatment intensities. The sensory stimulus reduced the LV closure time by 22.94% (P=0.027) and the LV opening time by 14.89% (P=0.009). Similarly, the motor treatment reduced the LV closure time by 38.26% (P=0.009) and the LV opening time by 10.85% (P=0.029). On the other hand, the UES opening time was not significantly reduced by the sensory stimulus (26.26%, P=0.108) but was reduced after the motor treatment (39.39%, P=0.009) (Figure 3). Hyoid motion: the maximum vertical and anterior extension was not changed by the surface electrical stimulation treatment at any of the intensities tested (Figure 4). In contrast, the time when the hyoid reached the maximal vertical extension was reduced significantly in both treatment groups (18.6% in the sensory group, P=0.036 and 24.8% in the motor group, P=0.008) and the time when the hyoid reached the maximal anterior extension was reduced after the motor treatment (33.8%, P=0.041) (Figure 4). Bolus kinematics: The sensory treatment did not significantly affect bolus velocity (from 0.241±0.035 m/s to 0.299±0.023 m/s, P=0.109) and bolus propulsion force (from 0.010 N before the treatment to 0.014 N after the treatment, P=0.148). In contrast, these parameters were significantly increased after the treatment at motor intensities: bolus velocity increased from 0.216±0.026 to 0.329±0.034 m/s (P=0.008) and bolus propulsion force from 0.009±0.002 N before the treatment to 0.019±0.003 N after the treatment (P=0.008).

Adverse Events Two adverse events were registered during the study (blood glucose increase and dental pain), both in the group of sensory stimulation, but none of them were considered serious nor related to the study intervention.

Figure 3. Temporal analysis of swallow. Timing of main events of the oropharyngeal swallow response during 5 mL swallows before (white bars) and after (grey bars) the treatment with surface electrical stimulation at sensory (left) and motor (right) intensities. A) Laryngeal vestibule closure time; B) Upper esophageal sphincter opening time; and C) Laryngeal vestibule opening time were determined. *P<0.05, **P<0.01.

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Motor vs sensory electrical stimulation in dysphagia

Figure 4. Maximal hyoid displacement times. Time of maximal vertical (A) and anterior (B) displacement of the hyoid bone during 5 mL swallows before (white bars) and after (grey bars) the treatment with surface electrical stimulation at sensory (left) and motor (right) intensities. * P <0.05, ** P <0.01.

Discussion The main conclusion of this study is that surface electrical stimulation is a safe and effective therapy for chronic OD associated to stroke. Surface electrical stimulation improved the swallow response and safety of swallow both at sensory and motor intensities, and the efficacy of swallow after the motor treatment. In addition, the therapy demonstrated an excellent safety profile as any serious adverse events related to the study product were detected. Since its approval in 2002, the e-stim therapy has been widely used, mainly in the USA. However, despite being well accepted by clinicians [25], the

therapy has also been widely criticized for not meeting evidence-based medicine criteria [26]. In the present study, we used two different therapeutic approaches of surface e-stim: on the one hand, we used a sensory intensity to stimulate the peripheral sensory system through thyro-hyoid electrodes to increase afferent drive and promote cortical plasticity and, on the other hand, the electrical stimulus was applied at the motor threshold with the electrodes placed in a sub-mental position to induce muscular contraction and improve hyoid motion and laryngeal protection. We selected the sub-mental position, as previous studies showed that electrodes at motor intensity placed in a thyro-hyoid position depress the hyolaryngeal complex, a movement in the opposite direction from

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Capítulo 7___________________________________________________________________ that required for swallowing [27;28]. The electrodes placed in the sub-mental region target the anterior belly of the digastric, the mylohyoid and the geniohyoid muscles, pulling the hyoid bone upward and toward the mandible [29], an action that facilitates airway protection and UES opening [24]. For the sensory therapy, the thyro-hyoid position was selected, as we aimed to target the laryngopharyngeal sensory afferents (the glossopharyngeal nerve and the superior laryngeal nerve) that carry the sensory input to the swallowing centre of the brainstem and to the cortical and sub-cortical structures. Patients included in the study presented chronic OD associated to stroke, advanced age, polymorbidity, and poor functional and nutritional status. Taken together, these conditions make patients vulnerable and at high risk of further complications, specifically for developing aspiration pneumonia, the major cause of mortality of stroke patients during the first year after discharge [4]. As spontaneous swallowing recovery is highly improbable at this stage of the disease, the treatment of dysphagia becomes a priority to improve the outcome of these stroke patients. The therapeutic effect of the treatment was clinically evaluated by means of two swallowing questionnaires and a videfluoroscopic study, the gold-standard method to assess swallowing function. Patients treated with the sensory stimulus presented an important improvement in the EAT-10 and the SSQ scores, even though they did not reach statistically significance, probably because of a low statistical power due to the small study sample. On the other hand, patients treated with the motor stimulus presented significant improvement in the SSQ but not in the EAT-10. The higher complexity of the SSQ versus the EAT-10 questionnaire can explain the better sensitivity to change of the questionnaire. One of the main results of the study is that 10 days of treatment at motor intensities reduced the prevalence of unsafe swallows of post-stroke dysphagic patients by accelerating the laryngeal vestibule closure time and the vertical hyoid movement. In addition, the treatment accelerated the anterior hyoid movement leading to the earlier opening of the UES which decreased the probability

of bolus overflow into the pharynx, and increased bolus propulsion forces, reducing the prevalence of oral and pharyngeal residues. These results show that swallow physiology can be improved by this treatment even in the chronic phase of stroke. Previous controlled studies evaluating the effect of surface e-stim at motor intensities in post-stroke patients found contradictory results [7;30-32]. While Freed and Lin reported greater swallowing function after the treatment with electrical stimulation when compared with thermal-tactile stimulation, Permsirivanich and Bulow reported no significant improvement of patients treated with e-stim when compared with traditional therapy (therapeutic maneuvers and techniques). These studies differed in the stimulation parameters used, such as number of sessions performed and electrode configuration, and only reported functional swallowing changes after treatment. Our study included physiological measures and reported how chronic e-stim changes the physiology of swallow leading to an improvement in the safety of swallow. In addition, the previous studies used concurrent stimulation of infra- and supra-hyoid muscles while we used only supra-hyoid stimulation, which, as discussed above, could be more suitable to treat these patients. The treatment with sensory stimulus also led to a strong improvement of the safety of swallow, similar to that presented by patients treated with motor stimulus, but did not significantly affect the efficacy of swallow. In a previous non-controlled study, Gallas et al [14] also reported that swallowing dysfunction could be improved using sensitive surface electrical stimulation. In that study, however, the sensory electrical stimulation was combined with swallowing exercises that could have been partly responsible for the observed effects. Even though the study of Gallas et al failed to demonstrate any effect of the therapy at cortical levels, previous studies using similar paradigms of peripheral sensory stimulation had. The application of an intrapharyngeal electrical stimulus increased the cortical excitability of dysphagic post-stroke patients that was strongly associated to an improvement of the swallowing behavior [13]. Our results suggest that impaired airway protection can be treated at sensory level. In contrast, the impairment in bolus transfer should be treated at motor intensities.

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Motor vs sensory electrical stimulation in dysphagia

The mechanisms underlying the efficacy of surface electrical stimulation in the treatment of post-stroke OD are not well known. It has been proposed that both peripheral and central modifications can be responsible for the effect of the therapy. At the peripheral site, modifications in muscle activation by the nervous system and/or alterations in muscle structure can occur and improve force production, coordination and precision of the contraction. Moreover, peripheral sensory nerves, that have a lower threshold of excitability compared with the sarcolemma surrounding muscle fibers, can also be activated and lead to cortical activation promoting both short-term and long-term neuroplasticity, facilitating deglutition and airway protection. We hypothesize that the improvement in safety of swallow achieved by the sensory stimulation is due to the stimulation of these peripheral pharyngeal and laryngeal sensory nerves. The greater effect observed when the stimulus was applied at motor intensities may be due to two reasons: on the one hand, the muscle contraction produced by the motor stimulus might lead to modifications in the suprahyoid muscles or their innervation that sensory stimulus could not achieve and, on the other hand, the higher intensity of the stimulus used in the motor group could lead to higher activation of the central nervous system structures. A dose-response relationship has been reported between the intensity of the peripheral nerve electrical stimulation and the intensity of activation of the primary sensory and motor cortex, cingulate gyrus and cerebellum, for the lower extremities of healthy subjects [33]. Although it remains unknown whether a similar dose-response relationship exists regarding pharyngeal stimulation in individuals with stroke, the greater activation of the cortical and subcortical areas together with muscle rehabilitation could explain the effects of the motor e-stim. Sensory e-stim, however, seems limited to neural controlled events and not to affect muscle strength.

control group. Even though spontaneous recovery of the swallowing function can be practically dismissed as patients were studied in the chronic phase of stroke, we did not compare our intervention with standard swallowing treatment, and therefore we cannot discount that similar results could not have been reached by the current therapeutic alternatives nor completely rule out the possibility of a “placebo effect”. Further large randomized controlled trials will be necessary to assess and evaluate the effect of the therapy on clinical outcome of patients for factors such as incidence of aspiration pneumonia, nutritional status and mortality rates. Moreover, neurophysiologic studies including the measurement of cortical excitability will be necessary to confirm the action mechanism of the therapy. In conclusion, our study shows that surface e-stim is a safe and effective therapy for chronic poststroke dysphagic patients, with specific effects on the safety and efficacy of swallowing. However, further investigation involving a control group, greater number of patients, prolonged follow-up and effect on clinical outcomes are needed to confirm the clinical utility of this therapy.

References

The absence of serious adverse events was also an important finding of the study, demonstrating that it is a safe and well tolerated therapy for dysphagia treatment. A limitation of the study was that it was designed as a quasi-experimental study (pre- post- treatment study) with a small sample size and without a

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1. Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-63. 2. Mann G, Hankey GJ, Cameron D. Swallowing function after stroke - Prognosis and prognostic factors at 6 months. Stroke 1999;30:744-8. 3. Clave P, de Kraa M, Arreola V, et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006;24:1385-94. 4. Katzan IL, Cebul RD, Husak SH, Dawson NV, Baker DW. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003;60:620-5. 5. Ickenstein GW, Riecker A, Hohlig C, et al. Pneumonia and in-hospital mortality in the context of neurogenic oropharyngeal dysphagia (NOD) in stroke and a new NOD step-wise concept. J Neurol 2010;257:1492-9.

Capítulo 7___________________________________________________________________ 6. Speyer R, Baijens L, Heijnen M, Zwijnenberg I. Effects of therapy in oropharyngeal dysphagia by speech and language therapists: a systematic review. Dysphagia 2010;25:40-65.

16. Gallas S, Marie JP, Leroi AM, Verin E. Sensory transcutaneous electrical stimulation improves post-stroke dysphagic patients. Dysphagia 2010;25:291-7.

7. Freed ML, Freed L, Chatburn RL, Christian M. Electrical stimulation for swallowing disorders caused by stroke. Respir Care 2001;46:46674.

17. Logemann JA. The effects of VitalStim on clinical and research thinking in dysphagia. Dysphagia 2007;22:11-2.

8. Carnaby-Mann GD, Crary AM. Adjunctive Neuromuscular Electrical Stimulation for Treatment-Refractory Dysphagia. Ann Otol Rhinol Laryngol 2008;117:279-87. 9. Blumenfeld L, Hahn Y, LePage A, Leonard R, Belafsky PC. Transcutaneous electrical stimulation versus traditional dysphagia therapy: A nonconcurrent cohort study. Otolaryngol Head Neck Surg 2006;135:754-7. 10. Jefferson S, Mistry S, Michou E, Singh S, Rothwell JC, Hamdy S. Reversal of a Virtual Lesion in Human Pharyngeal Motor Cortex by High Frequency Contralesional Brain Stimulation. Gastroenterology 2009;137:8419. 11. Park JW, Oh JC, Lee JW, Yeo JS, Ryu KH. The effect of 5Hz high-frequency rTMS over contralesional pharyngeal motor cortex in post-stroke oropharyngeal dysphagia: a randomized controlled study. Neurogastroenterol Motil 2013;25. 12. Kumar S, Wagner CW, Frayne C, et al. Noninvasive Brain Stimulation May Improve Stroke-Related Dysphagia A Pilot Study. Stroke 2011;42:1035-40.

18. Carnaby-Mann GD, Crary MA. Examining the evidence on neuromuscular electrical stimulation for swallowing: a meta-analysis. Arch Otolaryngol Head Neck Surg 2007;133:564-71. 19. Vellas B, Guigoz Y, Garry PJ, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition 2009;15:116-22. 20. Belafsky PC, Mouadeb DA, Rees CJ, et al. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol 2008;117:919-24. 21. Wallace KL, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of oral-pharyngeal dysphagia. Gastroenterology 2000;118:678-87. 22. Rosenbek J, Robbins J, Roecker E. A penetration-aspiration scale. Dysphagia 1996;11:93-8. 23. Burgos R, Sarto B, Segurola H, et al. Translation and Validation of the Spanish Version of the Eat-10 (Eating Assessment Tool-10) for the Screening of Dysphagia. Nutr Hosp 2012;27:2048-54.

13. Jayasekeran V, Singh S, Tyrrell P, et al. Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions. Gastroenterology 2010;138:1737-46.

24. Rofes L, Arreola V, Romea M, et al. Pathophysiology of oropharyngeal dysphagia in the frail elderly. Neurogastroenterol Motil 2010;22:851-8, e230.

14. Teismann IK, Steinstrater O, Warnecke T, et al. Tactile thermal oral stimulation increases the cortical representation of swallowing. BMC Neurosci 2009;10:71.

25. Crary MA, Carnaby-Mann GD, Faunce A. Electrical stimulation therapy for dysphagia: Descriptive results of two surveys. Dysphagia 2007;22:165-73.

15. Rofes L, Arreola V, Martin A, Clavé P. Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia. Gut 2012; in press (doi:10.1136/gutjnl-2011300753).

26. Geeganage C, Beavan J, Bath PMW. Interventions for dysphagia after stroke: a Cochrane systematic review. Int J Stroke 2012;7:40. 27. Humbert IA, Poletto CJ, Saxon KG, et al. The effect of surface electrical stimulation on

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Motor vs sensory electrical stimulation in dysphagia hyolaryngeal movement in normal individuals at rest and during swallowing. J Appl Physiol 2006;101:1657-63. 28. Ludlow CL, Humbert I, Saxon K, Poletto C, Sonies B, Crujido L. Effects of surface electrical stimulation both at rest and during swallowing in chronic pharyngeal dysphagia. Dysphagia 2007;22:1-10. 29. Kim SJ, Ryoon T. Effect of Surface Electrical Stimulation of Suprahyoid Muscles on Hyolaryngeal Movement. Neuromodulation 2009;12:134-40. 30. Bulow M, Speyer R, Baijens L, Woisard V, Ekberg O. Neuromuscular electrical stimulation (NMES) in stroke patients with oral and pharyngeal dysfunction. Dysphagia 2008;23:302-9.

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31. Lim KB, Lee HJ, Lim SS, Choi YI. Neuromuscular Electrical and Thermal-Tactile Stimulation for Dysphagia Caused by Stroke: A Randomized Controlled Trial. J Rehabil Med 2009;41:174-8. 32. Permsirivanich W, Tipchatyotin S, Wongchai M, et al. Comparing the effects of rehabilitation swallowing therapy vs. neuromuscular electrical stimulation therapy among stroke patients with persistent pharyngeal dysphagia: a randomized controlled study. J Med Assoc of Thai 2009;92:259-65 33. Smith GV, Alon G, Roys SR, Gullapalli RP. Functional MRI determination of a doseresponse relationship to lower extremity neuromuscular electrical stimulation in healthy subjects. Exp Brain Res 2003;150:33-9.

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DISCUSIÓN GENERAL

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- 136 -

Discusión general las alteraciones de seguridad y eficacia de la

DISCUSIÓN GENERAL

deglución que presentan. La presente Tesis Doctoral consta de un conjunto

-

de estudios clínicos, todos ellos publicados en

factor de riesgo para el desarrollo de CAP en el

revistas internacionales indexadas y con factor de

anciano y como factor de mal pronóstico clínico en

impacto, que han pretendido abordar de forma

el anciano frágil y en el anciano con CAP.

integrada

diferentes

aspectos

de

la

disfagia

orofaríngea en el paciente adulto, que van desde el estudio

diagnóstico

al

fisiopatológico,

y

con

especial énfasis, se centra en el desarrollo de nuevas estrategias terapéuticas para los pacientes con

disfagia

neurógena

y

asociada

al

Estudio de la disfagia orofaríngea como

En los Capítulos 4, 5, 6 y 7 se evalúan nuevas alternativas terapéuticas para el tratamiento de los pacientes

con

disfagia

orofaríngea.

Específicamente se evalúa: -

Un tratamiento compensador: efecto de los

envejecimiento. Cabe destacar que todos los

espesantes de goma xantana.

estudios de los que consta esta Tesis Doctoral se

-

han realizado utilizando la técnica patrón de oro

efecto del aumento del input sensorial a través de

para el estudio de la deglución, la videofluoroscopia

la adición al bolo alimentario de agonistas naturales

(VFS), permitiendo así una evaluación exhaustiva

de la familia de receptores TRP, y

de los mecanismos deglutorios y sus alteraciones en los diferentes grupos de pacientes estudiados y un análisis objetivo del efecto de los tratamientos. En los diferentes capítulos que forman esta Tesis Doctoral se han tratado los siguientes puntos:

de

Un

tratamiento

de

neuro-estimulación:

Un tratamiento neuro-rehabilitador: efecto dos

protocolos

de

estimulación

eléctrica

transcutánea (nivel de estimulación sensorial y motora) en pacientes con disfagia que han sufrido un ictus.

En el Capítulo 1, se presenta: -

La precisión diagnóstica de un cuestionario

de cribado (EAT-10) y un método de evaluación clínica para la disfagia orofaríngea (MECV-V). Hemos determinado la sensibilidad, especificidad y

Precisión diagnóstica de un cuestionario de cribado y un método de evaluación clínica para la DO

valores predictivos positivos y negativos de ambos

La disfagia es un trastorno del sistema digestivo

métodos frente al test de referencia, la VFS. Para el

específicamente clasificado por la WHO en la

cuestionario de cribado EAT-10 hemos establecido

International Statistical Classification of Diseases

el punto de corte de la puntuación del cuestionario

and Related Health Problems (ICD-10), recibiendo

para identificar a los pacientes con DO.

el código R13 para identificar su diagnóstico [1]. Sin

En los Capítulos 2 y 3, se aborda el:

embargo, a pesar de la alta prevalencia y las

-

Estudio de la fisiopatología deglutoria de

dos fenotipos de pacientes en riesgo de disfagia orofaríngea: el anciano frágil y el anciano con CAP. Se caracteriza el proceso deglutorio de estos pacientes

con

el

objetivo

de

identificar

las

alteraciones biomecánicas críticas que conducen a

graves consecuencias de la DO en el paciente anciano y en el paciente neurológico, la DO continúa siendo un trastorno infra-diagnosticado, y en consecuencia, infra-tratado [2,3]. Sin embargo, los métodos instrumentales de referencia para el estudio y el diagnóstico del trastorno deglutorio no

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Discusión general________________________________________________________________ están disponibles en todos los centros sanitarios.

requisitos necesarios para ser implementados en la

Además, el conocimiento del trastorno deglutorio

práctica clínica habitual del algoritmo diagnóstico

por parte del profesional sanitario es bajo, lo que

del paciente en riesgo de DO.

contribuye a una situación de desatención y falta de equidad al trato del paciente con DO. A pesar de que las guías de práctica clínica, por ejemplo de manejo del paciente con ictus, recomiendan la evaluación de la función deglutoria lo más pronto posible [4], la realidad es que las auditorías realizadas en nuestro país demuestran que sólo se realizan un 45.8% (IC 95% 42.7-48.8) de tests de disfagia válidos para evaluar la función deglutoria antes del inicio de la dieta o medicación oral en la fase aguda del ictus [5]. En contraposición a este hecho, se ha descrito que cuando se implementan programas estructurados que evalúan la presencia y tratan la DO en los hospitales y otros centros sanitarios, se reduce la incidencia de neumonía, los costos en antibióticos y las tasas de mortalidad de forma sistemática [6;7]. Por este motivo, es de especial interés el desarrollo de métodos de cribado y de evaluación clínica que puedan ser aplicados

de

forma

amplia

y

nos

permitan

seleccionar aquellos pacientes que deben ser derivados a realizarse la prueba instrumental o que nos permitan abordar su tratamiento en el caso que la prueba instrumental no esté disponible. Los métodos de cribado y evaluación clínica del paciente

con

DO

deberían

ser

sensibles,

específicos, de fácil y rápida administración, así como coste-efectivos [8]. En la literatura, hay disponibles una gran variedad de métodos de cribado y de evaluación clínica para la DO. La decisión de cuál de ellos debemos implementar y usar en la práctica clínica debería basarse en su fiabilidad,

validez, capacidad discriminatoria

y

propósito evaluativo [9]. En el Capítulo 1 de esta Tesis Doctoral hemos evaluado un cuestionario de cribado, el EAT-10, y un método de evaluación clínica, el MECV-V, que consideramos cumplen los

El proceso de cribado de la DO debería detectar aquel paciente en riesgo de padecer alteraciones deglutorias.

Para

el

profesional

sanitario

familiarizado con la disfagia este proceso puede llevarse a cabo mediante la anamnesis y la exploración física del paciente. Sin embargo, tal y como se ha mencionado anteriormente, la dificultad de

perfilar

orofaringea pacientes

el

conocimiento

dificulta en

la

riesgo.

de

la

identificación Es

aquí

disfagia de

los

donde

los

cuestionarios de síntomas deglutorios podrían tener su mayor aplicación, ya que de una manera rápida y sencilla podrían facilitar esta identificación al profesional sanitario que no está específicamente entrenado

en

especialmente

el

diagnóstico

aquellos

que

de se

la

disfagia,

enfrentan

a

poblaciones en las que la prevalencia de disfagia no es muy elevada como puede ser el ámbito de atención

primaria.

Cuando

buscamos

una

herramienta de cribado de primera línea en un proceso diagnóstico, la sensibilidad debe primar sobre la especificidad, ya que el interés principal es no dejar de diagnosticar ningún posible paciente afectado (no tener falsos negativos) a pesar de que aumentemos el ratio de falsos positivos, ya que el coste de no identificar un paciente con disfagia (factor de mal pronóstico tal y como se ha mostrado en

los

Capítulos

2

y

3

y

se

discutirá

posteriormente) es mucho mayor al de incluir un paciente sano en el proceso diagnóstico el cual podrá ser descartado con exploraciones posteriores más específicas y que comportan un mínimo riesgo. Este hecho es especialmente importante en una

enfermedad

con

complicaciones

potencialmente muy severas como es el caso de la DO. El cuestionario EAT-10 (ver Anexo 1) puede ser una buena alternativa en este proceso de

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Discusión general cribado gracias a la alta sensibilidad y PPV que

será la población final en la que será utilizado el

presenta.

permiten

test. Estos resultados confirman que el test posee

recomendar utilizar un punto de corte de 2 para

las características psicométricas adecuadas para

determinar aquellos pacientes en riesgo de disfagia

ser implementado en la práctica clínica. Además,

que deberían remitirse a un examen deglutorio más

se ha podido determinar la correlación entre

exhaustivo, a pesar de que en un estudio previo

evaluadores, parámetro que no se evaluó en el

[10] se recomendó utilizar un punto de corte de 3.

estudio inicial [15], y que ha sido considerada

Esta recomendación se fundamenta en dos grupos

buena. Nuestra principal conclusión es que el

de datos: primero, porque de acuerdo con los

MECV-V es un método que, si es aplicado por

resultados de la curva ROC (Receiver Operating

personal entrenado, ofrece unas características

Characteristic) disminuir el punto de corte de 3 a 2

óptimas para la detección y manejo del paciente

implica un aumento de sensibilidad de un 5% sin

con DO.

Nuestros

resultados

que disminuya la especificidad del test; y segundo, porque el punto de corte de 3 se estableció de

Fisiopatología de la DO en ancianos: el

referencia de una población sana (media + 2

fenotipo frágil y los ancianos con neumonía

desviaciones

adquirida en la comunidad

tomando

el

límite

superior

estándar),

del

el

intervalo

cual

se

puede

superponer con el límite inferior del intervalo en la población enferma, lo cual

puede llevar a la

clasificación errónea de pacientes con disfagia, con el riesgo que esto conlleva.

La prevalencia de disfagia orofaríngea en la población anciana es elevada. Se han reportado prevalencias que van desde el 11.4%- 33.7% en ancianos de la comunidad [16-18], de entre el 40-

El MECV-V es uno de los dos métodos de

51% en ancianos hospitalizados [19;20], y hasta el

exploración clínica, junto con el Toronto Bedside

55% de los ancianos hospitalizados con neumonía

Screening Test (TOR-BSST) [11],

[21]. El proceso natural de envejecimiento conduce

recomendados para la exploración de pacientes

a una pérdida progresiva de masa muscular y

neurológicos

revisión

fuerza, conocida como sarcopenia [22]. Además, el

sistemática [12]. La calidad metodológica de los

envejecimiento también se asocia a un proceso

estudios en los que se validaron estos dos

progresivo de neurodegeneración, tanto a nivel de

métodos,

características

sistema nervioso central como periférico. Esta

psicométricas, así como su aplicabilidad los hacen

pérdida de funcionalidad tanto de los elementos

superiores a tests ampliamente usados como el test

neuronales como musculares, acaba conduciendo,

del agua [13;14]. El estudio de validación del

entre otros, a cambios no patológicos en el proceso

MECV-V frente a VFS en la que se basa esta

deglutorio

revisión fue publicado en 1998 por Clavé et al [15].

cambios incluyen una disminución de la presión

En este nuevo estudio hemos re-validado el test

lingual isométrica y un enlentecimiento en el

utilizando

movimiento

de

ThickenUp Clear, Nestlé Health Science, Lausanne,

orofaríngeas

durante

Switzerland) y ampliado la población de estudio no

embargo, cuando esta pérdida de reserva funcional

limitándonos sólo a los pacientes neurológicos si no

se combina con otros factores como pueden ser

incluyendo también pacientes ancianos, ya que

diferentes co-morbididades y/ o sus tratamientos,

Swallowing

según

junto

un

una

con

nuevo

reciente

sus

espesante

(Resource

- 139 -

conocidos

las

como

presbifagia.

principales la

deglución

Estos

estructuras [23].

Sin

Discusión general________________________________________________________________ pueden conducir a un deterioro patológico del

estaba afectada en este grupo de pacientes,

proceso deglutorio y a la presencia de disfagia

reflejada por la alta prevalencia de residuo oral y

orofaríngea. El segundo objetivo de esta tesis ha

faríngeo. Se observó que el factor crítico que

sido la caracterización de las alteraciones de la

diferenciaba los pacientes con alteración de la

deglución en el anciano frágil [24] y en el anciano

eficacia de la deglución de los que presentaban

con neumonía adquirida en la comunidad (CAP),

deglución eficaz, además de un retraso en la

dos fenotipos de ancianos en especial riesgo de

respuesta motora orofaríngea, era especialmente

sufrir disfagia orofaríngea. Nuestro objetivo ha sido

una débil fuerza de propulsión del bolo alimentario.

identificar aquellos factores fisiopatológicos críticos

La fuerza de propulsión del bolo fue calculada

que conducen a las alteraciones de la seguridad y

mediante el análisis de las imágenes VFS, tal y

de la eficacia de la deglución en estos dos

como

fenotipos de pacientes para identificar aquellos

Actualmente estamos correlacionando en nuestra

puntos clave en los cuales deberíamos focalizar el

Unidad este método indirecto de evaluación de la

tratamiento de la disfagia para compensarlos o

fuerza de propulsión del bolo alimentario frente

revertirlos y así evitar las complicaciones que de

métodos directos de evaluación de la presión

ellos se derivan.

lingual (Iowa Oral Performance Instrument, IOPI).

En el estudio en pacientes ancianos frágiles

En resumen, hemos identificado los dos grandes

(Capítulo 2) observamos que, en efecto, este

factores responsables de la DO en estos dos

grupo poblacional presentaba un patrón motor

grupos de pacientes, factores a los que deberían

deglutorio retardado y prolongado, mostrando un

dirigirse los tratamientos para la disfagia: el primero

retraso en el cierre del vestíbulo laríngeo (LV) y en

de ellos, primordialmente de origen neurológico, es

la apertura del UES, así como una duración total de

el retraso en el cierre de la vía respiratoria, y el

la respuesta motora orofaringea mayor comparada

segundo de ellos, primordialmente de origen

con los voluntarios jóvenes. Presentaban además

muscular, la débil fuerza de propulsión del bolo

alteraciones en el movimiento del hioides y débil

alimentario.

fuerza de propulsión del bolo que vimos reflejada

encontrados en el grupo de pacientes ancianos con

en la baja velocidad de tránsito faríngeo. Estos

CAP (Capítulo 3). El 52.8% de estos pacientes

cambios en la fisiología deglutoria, conducen a

presentaron alteraciones de la seguridad, y del

alteraciones patológicas en nuestro grupo de

mismo modo que en el grupo de ancianos frágiles,

ancianos

signos

se relacionaron con un retraso en el cierre del

videofluoroscópicos), grupo con alto número de co-

vestíbulo laríngeo y en el movimiento vertical del

morbididades y síndromes geriátricos: hasta el

hioides. Estudios anteriores realizados por nuestro

57,1% presentaron penetraciones en el LV y un

grupo en pacientes neurológicos [25;26], también

17,1%

de

encontraron que el tiempo que transcurría entre la

líquidos. Pudimos observar que el factor clave que

apertura del selllo glosopalatino y el cierre del LV

determinaba la presencia de alteraciones de la

era el predictor principal de la presencia de

seguridad de la deglución era un retraso en el

penetraciones y aspiraciones. Ambos estudios

cierre del vestíbulo laríngeo, y en menor medida un

identificaban también el retraso en la apertura del

movimiento vertical del hioides también retardado.

UES como un factor clave que condiciona la

Por otro lado, la eficacia de la deglución también

seguridad de la deglución. Sin embargo, en

frágiles

(evidenciadas

aspiraciones

durante

la

como

deglución

- 140 -

se

ha

descrito

Resultados

en

la

Introducción.

similares

fueron

Discusión general nuestros estudios con ancianos el retraso en la

fenotipos de ancianos pueden conducir a graves

apertura del UES no se asoció con alteraciones de

complicaciones: la alteración de la eficacia de la

la seguridad. Es cierto que un retraso en la apertura

deglución se asocia a la presencia de malnutrición

del UES puede ocasionar el acumulo del bolo

y la alteración de la seguridad, al desarrollo de

alimentario en la hipofaringe que puede llegar a

infecciones respiratorias [27].

rebosar a la vía respiratoria, causando aspiraciones durante la deglución y por otro lado, incrementar el residuo faríngeo, lo que contribuye al desarrollo de aspiraciones post-deglutorias. En nuestros estudios actuales, las penetraciones/ aspiraciones que ocurren durante la deglución son las que hemos observado con mayor frecuencia.

La disfagia y sus complicaciones son factores íntimamente ligados que se retroalimentan: las alteraciones deglutorias aumentan el riesgo de malnutrición

y

de

aparición

de

infecciones

respiratorias; la malnutrición es un factor que se ha asociado al desarrollo de sarcopenia, fragilidad y alteración del sistema inmunológico en el anciano. Estos factores cierran el círculo empeorando aún

La DO como factor de riesgo para el desarrollo

de

CAP

y

factor

de

mal

pronóstico en el anciano frágil y en el anciano con CAP

más el trastorno deglutorio y el estado nutricional, y aumentando el riesgo de infecciones respiratorias (Figura

1).

Todos

estos

factores

que

se

retroalimentan entre ellos forman un círculo vicioso que se asocia a una alta mortalidad.

Las alteraciones de la seguridad y de la eficacia de la deglución que hemos descrito en estos dos

Figura 1: Fisiopatologia de las complicaciones nutricionales y respiratorias asociadas a la disfagia orofaríngea en el anciano. Adaptado de: Rofes et al 2011 [27].

- 141 -

Discusión general________________________________________________________________ La relación entre DO y neumonía aspirativa (AP)

de forma independiente con la CAP después de

está bien establecida en el anciano [28;29], es más,

ajustar por los diferentes factores de confusión

muchos autores consideran el riesgo de aspiración

(capacidad

condición sine qua non para el diagnóstico de la AP

cardíaca). Puede ser discutible que la evaluación

[30;31]. Así pues, la alteración de la seguridad de la

deglutoria en este estudio se realizase durante el

deglución, junto con la colonización de la orofaringe

ingreso de los pacientes, momento en el cual

por bacterias patógenas (a menudo consecuencia

podrían presentar un declive funcional transitorio

de una mala higiene oral) y la alteración del sistema

que

inmune (frecuentemente asociada a malnutrición),

complicando el establecimiento de la relación de

conforman los tres pilares básicos que explican la

causalidad. Sin embargo, en un estudio de cohortes

patogenia de la AP. Sin embargo, la alta incidencia

realizado en una población de unas características

de CAP en el anciano no se asocia en la práctica

similares a las estudiadas (ancianos viviendo de

clínica habitual a la existencia de un trastorno

forma independiente en la comunidad), después de

deglutorio, a pesar de que algunos estudios han

un año de seguimiento encontraron que las

apuntado

alteraciones de la seguridad de la deglución se

su

relación

[32-34],

sino

que

funcional,

magnificase

alteración

alta

infecciones de las vías respiratorias inferiores [37],

co-morbididades

y/o

avanzada. La alta prevalencia de DO en el anciano,

deglutoria sería la causa, y no la consecuencia de

especialmente en los ingresados con neumonía

la CAP, y de que, tal y como apuntaban Teramoto

[21], debería llevarnos a pensar que una gran parte

et al [36] en su estudio, una gran parte de las CAP

de las CAP en esta población podría tener etología

en el anciano podrían ser de etiología aspirativa y

aspirativa, pero la literatura existente al respecto

la DO podría jugar un papel muy relevante en su

presenta importantes discordancias [35;36]. El

patogenia.

de

casos-controles

realizado

para

determinar si la disfagia orofaríngea podría ser un factor de riesgo de CAP en ancianos. Para determinar la presencia de DO, tanto los casos como los controles fueron estudiados de forma prospectiva mediante el MECV-V [15]. Éste es un dato

importante

ya

que

en

los

estudios

epidemiológicos previos, la relación entre CAP y DO se había realizado utilizando registros clínicos o sistemas

de

evaluación

no

validados

para

determinar la presencia de DO. Al ser la DO un trastorno poco reconocido y considerado, puede llevar al infra-diagnóstico del trastorno deglutorio en pacientes con CAP [32;33]. Y efectivamente, el análisis multivariado mostró que la DO se asociaba

que

la

de

favoreciendo

estudio

hipótesis

incidencia

enfermedades crónicas en esta población de edad

Capítulo 3 de esta Tesis Doctoral incluye un

la

mayor

deglutoria,

relacionaban

de

una

insuficiencia

habitualmente se considera la consecuencia de la prevalencia

con

la

COPD,

alteración

Del mismo modo, en el estudio en ancianos frágiles (Capítulo 2), también evaluamos si los trastornos deglutorios podrían ser un factor de mal pronóstico clínico. En ancianos frágiles, tanto la alteración de la seguridad como de la eficacia de la deglución se asociaron con unos índices de mortalidad al año significativamente superiores a los de los ancianos que no presentaron estas alteraciones deglutorias. En el caso de los ancianos que fueron ingresados con CAP, la alteración de la seguridad de la deglución también se asoció con una mayor mortalidad al año. El peor estado funcional, la mayor presencia de co-morbididades e índices de fragilidad en aquellos pacientes con disfagia podrían contribuir al peor pronóstico observado; sin embargo, un estudio realizado en nuestro centro en

- 142 -

Discusión general mayores de 80 años ingresados en la Unidad

sufrido un ictus concluyó que no existe evidencia

Geriátrica de Agudos, en que se ajustó la

suficiente para determinar si las terapias existentes

supervivencia

co-

tienen un efecto significativo en la evolución clínica

disfagia

del paciente o sobre la tasa de mortalidad asociada

orofaríngea era un factor de mal pronóstico

a la DO. Ambas revisiones concluyen que es

independiente [21]. En pacientes que han sufrido

necesario realizar estudios clínicos adicionales con

un ictus el trastorno deglutorio también se ha

un buen diseño metodológico para generar un nivel

asociado a un mayor riesgo de sufrir neumonía por

de evidencia mayor que justifique la utilización de

aspiración [38], lo cual también se asocia a un

los tratamientos actuales así como desarrollar

mayor riesgo de mortalidad [39].

nuevas alternativas terapéuticas más eficaces,

morbididades,

por

edad,

determinó

funcionalidad que

la

y

diseñadas

para

combatir

específicamente

las

alteraciones fisiopatológicas del paciente con DO.

Nuevas alternativas terapéuticas para el paciente con disfagia orofaríngea

Gran parte del trabajo desarrollado durante esta Tesis Doctoral, una vez caracterizado el patrón

La necesidad de intervención para romper el círculo

fisiopatológico del paciente anciano con DO y

descrito en la Figura 1 se hace evidente. A pesar

evaluado

de la relevancia clínica de la DO, las alternativas

pueden ayudar a su identificación, se ha centrado

terapéuticas de las que disponemos para su

precisamente

tratamiento son escasas. Además, la evidencia

terapéutica del trastorno deglutorio, tanto mediante

científica existente hasta el momento de la eficacia

estrategias compensatorias (nueva generación

de dichos tratamientos es limitada. Speyer et al [40]

de espesantes), como mediante tratamientos

concluían en su revisión sistemática de los efectos

activos (neuro-estimulación mediante estímulos

de la terapia administrada por logopedas en la

químicos o eléctricos). En la Tabla 1 se muestra un

disfagia orofaríngea que, a pesar de que la mayoría

resumen del efecto terapéutico de las diferentes

de estudios reportaban efectos significativos, las

estrategias evaluadas en los estudios incluidos en

conclusiones no podían generalizarse debido al

esta Tesis Doctoral en los diferentes fenotipos de

bajo número de estudios existentes y algunos

pacientes con DO estudiados. La tabla no pretende

problemas metodológicos de los mismos. Una

ser una comparación directa de las diferentes

reciente revisión Cochrane [41] en la que se evaluó

estrategias estudiadas, ya que las poblaciones en

la efectividad de diferentes intervenciones para el

las que se han evaluado son distintas, pero sí

tratamiento de la disfagia en pacientes que habían

pretende ser una guía que facilite su discusión.

- 143 -

dos

herramientas en

el

objetivo

diagnósticas de

mejorar

que la

Discusión general

Efectos de los tratamientos sobre la seguridad

consigue con viscosidad pudín, con la cual

de la deglución

conseguimos un significativo descenso tanto del

Tradicionalmente, en pacientes que presentan penetraciones

en

el

vestíbulo

laríngeo

o

aspiraciones cuando degluten líquidos, se han utilizado espesantes para aumentar su viscosidad y así incrementar la seguridad de la deglución. A pesar de ser una práctica generalizada en el tratamiento de los pacientes con DO, el número de estudios que evalúan específicamente su efecto terapeútico es limitado [25;42;43] por

lo que la

evidencia científica de la eficacia de los espesantes es escasa [40]. Además, la falta de consenso en cuanto

a

características

la

nomenclatura, de

los

definición

y

niveles

de

diferentes

modificación de la viscosidad de los líquidos, dificulta

aún

más

la

generalización

de

los

resultados obtenidos y la evaluación objetiva del efecto de la terapia. En los últimos tiempos se está trabajando en este sentido y han surgido diferentes iniciativas como la International Dysphagia Diet Standarisation Innitiative (http://iddsi.org/) que tiene como

objetivo

desarrollar

definiciones

estandarizadas para la modificación de la textura de los alimentos y de los líquidos espesados para personas con disfagia de todas las edades y culturas y en todos los ámbitos de atención [44] o el documento de posición que está elaborando la

número de penetraciones como de aspiraciones. Cuando

utilizamos

un

espesante

de

goma

xantana (Capítulo 4) también obtuvimos un efecto terapéutico máximo con la viscosidad pudín, sin embargo, el néctar conseguido con este espesante parece tener un efecto terapéutico mucho mayor que el que obtuvimos con el espesante de almidón. Este es un dato relevante ya que, el conseguir proteger a más pacientes con unas viscosidades bajas, podría incrementar la adherencia terapéutica al tratamiento, la cual es baja [45]. No obstante, debemos decir que para sacar conclusiones definitivas, sería necesario un estudio comparativo de los dos espesantes en el mismo grupo de pacientes. Este aumento de la seguridad de la deglución

observado

con

los

dos

tipos

de

espesantes a viscosidad néctar, no se relacionó sin embargo con un cambio en aquellos parámetros que detectamos que eran claves para determinar la seguridad de la deglución (tiempo de cierre del vestíbulo laríngeo y tiempo de extensión máxima vertical del hioides), ya que ninguno de ellos se modificaba con el aumento de la viscosidad en los pacientes con DO, lo que nos indica que los espesantes protegen al paciente mediante un mecanismo compensatorio. Se ha propuesto que el principal mecanismo de acción de los espesantes

European Society for Swallowing Disorders.

es disminuir la velocidad a la que viaja el bolo por la En esta Tesis Doctoral hemos descrito que el aumento de la viscosidad del bolo con un espesante

de

almidón,

aumenta

significativamente la seguridad de la deglución en pacientes ancianos (Capítulos 2 y 5) de una forma concentración-dependiente.

Podemos

observar

como aumentar la viscosidad del bolo hasta néctar, es

suficiente

para

evitar

casi

la

mitad

de

aspiraciones que se producían con líquido, sin embargo, sólo se reducen ligeramente el número

faringe [46], proporcionando así el tiempo necesario para que se cierre la vía respiratoria en condiciones de seguridad. En efecto, hemos podido observar que esta premisa se cumple en los dos espesantes cuando se utiliza viscosidad pudin. Sin embargo, a viscosidad néctar, no se produce una disminución significativa de la velocidad, lo cual nos estaría indicando que las propiedades intrínsecas del bolo espesado

serían

responsables

del

efecto

terapéutico observado, evitando las aspiraciones y

de penetraciones. El máximo efecto terapéutico se

- 145 -

Discusión general________________________________________________________________ penetraciones, sin cambiar la fisiología deglutoria.

suplementarlo con los agonistas TRPV1 sí se

En este estudio controlamos la viscosidad de los

produjeron cambios en la RMO de los pacientes

fluidos administrados, sin embargo, existen otras

con DO: el LV se cerró antes, y por lo tanto, se

propiedades

cohesividad,

consiguió una protección de la vía respiratoria más

adhesividad o gomosidad que pueden también

temprana evitando las penetraciones observadas

influenciar en sus propiedades terapéuticas y que

en el bolo control. La capsaicina, además, aceleró

deberán evaluarse en posteriores estudios. Otro

el movimiento vertical del hioides.

como

la

dureza,

dato importante a discutir que se obtuvo del estudio del efecto de los espesantes de goma xantana en la fisiología deglutoria (Capítulo 4), es el hecho de que los voluntarios sanos y los pacientes con disfagia pero sin alteración de la seguridad de la deglución,



reconfiguración

son

capaces

del

sistema

características del

de

adaptar

deglutorio

a

la las

bolo: de este modo, cuando

degluten un líquido o un néctar, que viaja a velocidades altas por la faringe, cierran el vestíbulo laríngeo antes que cuando degluten un pudín, que viaja a velocidades bajas. La inexistencia de este feedback sensorial - motor que permite adaptar la respuesta motora orofaríngea a las características del bolo podría ser uno de los responsables de la presencia de alteraciones de la seguridad en pacientes con DO. Una vez más, se pone de manifiesto la importancia del estímulo sensorial en la regulación de la función deglutoria y cómo su alteración

se

relaciona

con

alteraciones

biomecánicas que conducen a la presencia de degluciones inseguras e ineficaces.

La e-stim trans-cutánea, por su lado, también aumentó la seguridad de la deglución, en este caso, en un grupo de pacientes con DO crónica asociada a ictus. Anteriormente, Clavé et al [25] habían

descrito

las

principales

alteraciones

fisopatológicas en este grupo poblacional, que, de forma similar a lo que hemos descrito en ancianos frágiles, se caracterizan por alteraciones tanto en la eficacia como en la seguridad de la deglución. Es interesante destacar que, a diferencia de lo que se podría esperar, el tratamiento tuvo efectos similares en cuanto a la mejora de la seguridad de la deglución, tanto a intensidad sensorial como motora. Al igual que con la capsaicina, esta mejora se produjo gracias al significativo acortamiento en el tiempo de cierre del LV y a una aceleración en el movimiento del hioides. El hecho de que estos acontecimientos se modifiquen de forma similar en ambas intensidades, nos podría estar indicando que son fenómenos que están básicamente bajo control neural, son altamente dependientes del input sensorial orofaríngeo y poco dependientes de

Para favorecer este feedback, quisimos comprobar

la mejora en el rendimiento muscular. Estudios

la hipótesis que el incremento del input sensorial

previos con e-stim trans-cutánea e intrafaríngea a

mediante

intensidades

agonistas

del

receptor

TRPV1

sensoriales

mostraron

efectos

(capsaicina y piperina), favorecería la respuesta

similares en la mejora de la seguridad de la

motora deglutoria en los pacientes con alteraciones

deglución que las observadas en nuestros estudios

de la seguridad de la deglución. Y efectivamente,

[47;48], y si bien el estudio de Gallas et al [47] falló

pudimos observar como mediante ambos agonistas

al relacionar estos cambios con modificaciones en

se reducía la prevalencia de penetraciones en el LV

la excitabilidad cortical evaluada mediante TMS,

al compararlo con un bolo de la misma viscosidad.

Jayasekeran et al [48] sí que observaron que la

A diferencia de lo ocurrido cuando se aumentaba la

mejora

viscosidad

estimulación

del

bolo

con

espesantes,

al

- 146 -

en

los

parámetros

eléctrica

deglutorios

intra-faríngea

tras

estaban

Discusión general

la

Dentro de las estrategias de neuro-estimulación

excitabilidad de la corteza motora faríngea también

periférica, la capsaicina, además de mejorar la

evaluada mediante TMS.

seguridad de la deglución, también mejoró la

fuertemente

asociados

a

incrementos

en

En resumen, las diferentes estrategias terapéuticas evaluadas mejoran la seguridad de la deglución mediante

dos

espesantes compensatorio

mecanismos utilizan con

principales:

un

los

mecanismo

efecto

secuencial:

a

viscosidades bajas no se produce ningún cambio en la fisiología deglutoria y son las propiedades intrínsecas del bolo las que favorecen la protección de la vía respiratoria; a viscosidades altas, además, disminuyen la velocidad del bolo por la orofaringe. De este modo, compensan el retraso en el cierre de la vía respiratoria que presentan los pacientes con DO. Por otro lado, los agonistas TRPV1 y la estim

transcutánea

actúan

revirtiendo

la

disfunción presente, acelerando el cierre del

eficacia, reduciendo el residuo faríngeo. Este fenómeno,

embargo,

no

ocurrió

cuando

utilizamos el otro agonista TRP, la piperina. En este caso, el efecto producido por el agonista fue puramente neurológico, sólo se vio afectada la temporalidad de los eventos ocurridos sin que se produjese ninguna alteración en la eficacia de los mismos. Este fenómeno merece ser discutido específicamente puesto que nuestra hipótesis inicial nos hacía esperar un mayor efecto de la piperina, basándonos en dos premisas: en primer lugar, las observaciones realizadas in vitro sobre el efecto de ambos agonistas sobre el TRPV1, que han determinado que a pesar de que la piperina es menos potente que la capsaicina en activar el receptor

vestíbulo laríngeo para proteger la vía respiratoria.

sin

(necesita

mayor

concentración

para

alcanzar el mismo efecto), es más eficiente (el efecto máximo alcanzado es mayor) [49;50]; y en Efectos de los tratamientos sobre la eficacia de

segundo lugar, que al ser la piperina un agonista

la deglución

dual TRPV1/ TRPA1, podría esperarse una mayor

A pesar del elevado efecto terapéutico del aumento de la viscosidad, los espesantes de almidón presentan un importante efecto indeseable, y es que

aumentan

el

residuo

orofaríngeo,

principalmente a viscosidad pudin (viscosidad a la cual presentan el mayor efecto terapéutico). Este residuo que permanece en la faringe después de la deglución pone al paciente en riesgo de presentar aspiraciones post-deglutorias, una vez finaliza la apnea deglutoria. Con el uso de espesantes de goma xantana no se observa un incremento significativo de residuo al incrementar la viscosidad, a pesar de que las viscosidades finales utilizadas son comparables a las obtenidas con almidón, lo cual le confiere a este tipo de espesantes una clara ventaja terapéutica frente a los de almidón.

activación de los terminales nerviosos. Una posible explicación a este fenómeno podría ser que en el estudio

de

la

capsaicina,

se

utilizó

para

suplementar el bolo, una mezcla natural de capsaicina y otros capsaicinoides que le confirieron al bolo final un pH ácido, a diferencia del bolo control. Es conocido que los H

+

son también

agonistas del TRPV1 y sensibilizan además el receptor a la acción de la capsaicina [51]. Estudios anteriores han determinado que el ácido es también un estimulante de la deglución [52] y que las presiones linguales generadas al deglutir un bolo ácido

son

mayores

en

comparación

de

las

presiones generadas con agua [53], lo cual podría ser responsable, al menos en parte, de la mayor eficacia observada al deglutir el bolo acidificado.

- 147 -

Discusión general________________________________________________________________ En cuanto a la e-stim transcutánea, sí que

y la e-stim a intensidad sensorial no afectan a la

observamos diferencias significativas en el efecto

eficacia de la deglución. Aumentar la viscosidad

de ambas intensidades sobre la eficacia de la

con espesantes de goma xantana, no aumenta el

deglución. Tal y como se ha discutido en el

residuo orofaríngeo, a diferencia de cuando se

Capítulo 7, nuestra hipótesis es que esta diferencia

utilizan espesantes de almidón, que aumentan de

puede deberse a dos fenómenos principalmente:

forma significativa el residuo, sobre todo a

por un lado, a que la facilitación de la contracción

viscosidad pudin.

muscular producida durante el tratamiento a intensidades motoras favorezca el rendimiento de la musculatura suprahioidea y por otro lado, que al estar aplicando una intensidad eléctrica mayor, la

Efectos adversos y perfil de seguridad de los tratamientos evaluados

activación de las estructuras sensoriales corticales

No menos importante que el efecto terapéutico de

sea también mayor y por lo tanto también los

las

efectos consecuencia de esta activación. Es

seguridad de las mismas, que debe también ser

importante destacar también, que el tratamiento de

evaluada

e-stim fue administrado con el paciente en situación

aplicabilidad.

de reposo. Si bien la e-stim transcutánea después de un ictus es un tratamiento rehabilitador habitual que suele administrarse durante los ejercicios de rehabilitación, la e-stim para la rehabilitación de la disfagia merece una atención especial. Si bien el fabricante del electroestimulador recomienda la aplicación de la terapia mientras se practican ejercicios deglutorios, nuestra opinión es que el hecho de deglutir de forma continuada durante el tratamiento cuando el paciente tiene alteraciones de la seguridad de la deglución, es decir, presenta aspiraciones,

puede

conducir

a

graves

complicaciones derivadas del mismo. Es en este sentido que consideramos que es de una gran importancia conseguir mejorar la seguridad de la deglución sin la necesidad de que el paciente degluta de forma continuada y por lo tanto, aumente el riesgo de aspirar y contraer una infección respiratoria. En

resumen,

de

diferentes

estrategias

rigurosamente

diferentes

estrategias

para

es

discutir

la

su

Los espesantes de almidón comercializados en España y financiados por el Sistema Nacional de Salud para la prevención y tratamiento de las aspiraciones en el paciente con DO, gozan de un perfil de seguridad reconocido. Sin embargo, existen algunos aspectos a tener en cuenta en referencia a su uso en pacientes con DO. A pesar de que la biodisponibilidad del agua no se altera con el uso de espesantes [54;55], el consumo diario de agua sí que puede disminuir en pacientes que toman líquidos espesados [56], lo que podría conducir, contrariamente a lo que se pretendía, a un estado de deshidratación. Además, se ha descrito que los líquidos espesados calman menos la sensación de sed que los líquidos sin espesar y que los espesantes pueden alterar la liberación y absorción

de

(especialmente

determinados los

Biopharmaceutics las

evaluadas,

de

la

fármacos Clase

Classification

III

[57] de

System

la of

medications (BCS) [58], como por ejemplo Atenolol,

terapéuticas evaluadas y en referencia al efecto

Captopril,

sobre la eficacia de la deglución, sólo la capsaicina

Amoxicilina,

y la e-stim transcutánea a intensidad motora

consecuencia, la acción de los mismos. En una

mejoran la eficacia de la deglución. La piperina

población altamente polimedicada como suelen ser

- 148 -

Cimetidina, Eritromicina)

Aciclovir, y

Penicilina,

afectarse,

en

Discusión general

los pacientes que sufren disfagia, este es un

también que los canales TRP tienen un amplio

importante punto a tener en cuenta y que requiere

patrón de expresión en todo el cuerpo y que están

ser evaluado rigurosamente.

involucrados en una amplia gama de procesos que

La goma xantana es un aditivo alimentario de uso común que goza también de un perfil de seguridad adecuado para su uso generalizado y sin restricción en humanos [59]. En nuestro estudio con los espesantes de goma xantana no se detectaron efectos adversos graves relacionados con el producto en estudio, ya que las alteraciones gastrointestinales

registradas

(mayoritariamente

deposiciones blandas) es un efecto secundario bien conocido del contraste radiológico utilizado en las

van desde la osmorregulación a la señalización térmica, química y sensorial, y potencialmente están también asociados a la fisiopatología de varias

enfermedades,

intestino

irritable,

la

como

el

síndrome

enfermedad

por

del

reflujo

gastroesofágico y la tos crónica. Esta situación hace que exista un riesgo potencial de efectos adversos y que sea necesario tener en cuenta estos datos a la hora de diseñar un posible tratamiento crónico de la DO con capsaicina [61].

exploraciones. Se produjo también un caso de

La piperina, por su lado, es considerado un

broncoaspiración que fue considerado un efecto

alimento GRAS (Generally recognized as safe) por

adverso grave pero no relacionado con el producto

la FDA [62], por lo que la suplementación de la

en estudio sino con el procedimiento diagnóstico

comida con esta sustancia es considerada segura.

utilizado en el paciente.

Sin embargo, se ha descrito que el consumo

Para realizar el estudio con capsaicina, optamos por utilizar los capsaicinoides naturales de un producto alimentario comercializado desde 1868 (Tabasco), que nos aseguraran realizar el ensayo en las mayores condiciones de seguridad posibles. A pesar de ser un estudio agudo y de que las cantidades de capsaicina administrada serían mínimas, se optó por la opción conservadora de utilizar un producto con un perfil de seguridad probado. En nuestro estudio no se detectó ningún efecto

adverso

grave

relacionado

con

la

administración de la salsa de capsaicinoides. Sin embargo, es conveniente tener en cuenta que consumos altos de capsaicina (25-200 mg/día) se han asociado a mayor prevalencia de cáncer del tracto digestivo alto, principalmente cáncer gástrico [60]. Sin embargo, consumos moderados de capsaicina (1.5 mg/día), similares a las dosis de capsaicina que estamos usando actualmente y que

crónico de cantidades elevadas de piperina (1.5 g/día) podría producir daños en la mucosa gástrica [63]. Debemos también tener en cuenta que la piperina es un inhibidor del citocromo P450 3A4 (CYP3A4), importante enzima involucrada en el metabolismo

de

xenobióticos

y

principal

responsable de la metabolización de los fármacos [64].

Debido

a

este

efecto

inhibitorio

del

metabolismo de fármacos, la piperina puede incrementar

la

biodisponibilidad

de

estos

compuestos y por lo tanto, deberían tomarse las precauciones adecuadas a la hora de diseñar un posible tratamiento crónico de la DO con piperina. En nuestro estudio en el que se evaluó el efecto agudo de la piperina, se detectó un efecto adverso leve (dolor abdominal autolimitado) en un paciente del grupo al que se le administró piperina 1 mM, el cual no fue considerado ni grave ni relacionado con la sustancia en estudio.

podrían usarse en un tratamiento crónico de la

La e-stim transcutánea, ha sido una terapia

disfágia (1.4 mg/día), no han mostrado esta

controvertida, tanto desde el punto de vista de la

asociación [60]. Tenemos que tener en cuenta

eficacia como de la seguridad, desde su aprobación

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Discusión general________________________________________________________________ por la FDA en 2001 [65]. Desde el punto de vista de

evalúen específicamente el impacto de la terapia

la seguridad, VitalStim no recomienda su uso sobre

en la evolución clínica del paciente.

procesos infecciosos activos y neoplasias activas, así como recomienda su uso con precaución en pacientes que sufran trastornos convulsivos, con aparatos electrónicos implantados (por ejemplo marcapasos), con demencia avanzada o con reflujo gastroesofágico. Todos estos supuestos fueron considerados, por precaución, criterios de exclusión en nuestro estudio. Además, los electrodos no deben ser colocados sobre el seno carotideo por riesgo de que se desencadene una bradicardia sinusal, y el hecho que se estimulen las aferencias laríngeas conlleva que exista un cierto riesgo de que se desencadene un laringoespasmo. Pocos son los estudios que han evaluado la seguridad de la e-stim transcutánea en el tratamiento de la DO, y los efectos adversos más frecuentes reportados son irritación de la piel y sensación de quemazón en la zona de aplicación de los electrodos, dolor de

En resumen, solo los espesantes presentan un perfil de seguridad adecuado para ser aplicados sistemáticamente en la práctica clínica habitual. Nuestra experiencia demuestra que la e-stim transcutánea es un tratamiento seguro y que a pesar de que son necesarios nuevos estudios que confirmen su eficacia clínica y establezacan el régimen terapeútico más adecuado, su uso en la clínica puede ser considerado en pacientes con DO crónica post-ictus dado que no existen alternativas terapeúticas

con

un

perfil

de

seguridad

significativamente superior. La seguridad de los agonistas

TRPV1

exhaustivamente comprendan

en

mayor

debe estudios número

ser

evaluada

adicionales de

que

pacientes

y

evaluaciones a largo plazo, antes de que puedan ser implantadas de forma sistemática en pacientes con DO.

cabeza, mandíbula y cuello, sensación de plenitud gástrica, tos y expectoración [66]. En nuestro estudio, detectamos dos efectos adversos en el grupo de pacientes que recibió e-stim a intensidad sensorial

(dolor

dental

y

aumento

en

la

concentración sanguínea de glucosa), los cuales no fueron considerados ni graves ni relacionados con la terapia. Debido a la limitada evidencia científica existente de la seguridad y la eficacia de la terapia, organismos como el británico National Institute for Health and Care Excellence, en su emisión preliminar de las NICE guidelines recomienda la realización de estudios adicionales de calidad que evalúen su seguridad y eficacia [67]. Nuestro estudio

apoya

el

hecho

de

que

la

e-stim

transcutánea es un tratamiento seguro y eficaz para el tratamiento de la DO asociada al ictus, pero cierto es que son necesarios estudios adicionales que confirmen los resultados encontrados y que

Perspectivas de futuro Durante décadas los tratamientos para la disfagia orofaríngea se han centrado en compensar la disfunción deglutoria a través de la adopción de diferentes

posturas

y

maniobras

durante

la

deglución. Estos tratamientos son ampliamente aceptados en la práctica clínica, pero la evidencia de

su

efectividad

en

la

DO

asociada

al

envejecimiento o enfermedades neurológicas es limitada, y los pacientes y cuidadores a menudo tienen dificultades de aprendizaje, enseñanza y/o realización de estas estrategias correctamente [40;68;69]. Las modificaciones de la dieta, tales como el aumento de la viscosidad de los fluidos, han tenido más éxito en la reducción de las aspiraciones y las penetraciones [25] y en la prevención de la neumonía por aspiración [43]. Sin embargo, los espesantes pueden modificar el

- 150 -

Discusión general

sabor de algunas bebidas [70], tienen una baja

concepto.

adherencia terapéutica [71] y no mejoran la

aleatorios que exploren poblaciones más grandes y

fisiología de la respuesta deglutoria. A pesar de ser

los efectos a largo plazo de estas estrategias. La

un tratamiento compensador, el uso de espesantes

relación entre los canales TRP y la disfagia abre un

continuaría siendo de elección en aquellos casos

nuevo

en que no existan posibilidades de rehabilitación o

estrategias farmacológicas para el tratamiento de la

cómo tratamiento concomitante durante el proceso

disfagia orofaríngea, aunque se necesita mucha

rehabilitador. De ahí la importancia de desarrollar

más investigación en este campo. Los efectos

productos que mejoren las propiedades de los que

centrales de los estimulantes farmacológicos no

tenemos disponibles en la actualidad. La nueva

están explorados prácticamente y hay muy pocos

generación de espesantes basados en goma

datos sobre los efectos de estos productos en

xantana

términos de la neuroplasticidad cortical, campo que

ofrece

unas

buenas

perspectivas

terapéuticas tal y como se ha descrito en el Capítulo

4.

Deberá,

no

obstante,

evaluarse

también si mejoran la adherencia al tratamiento, factor clave en el éxito terapéutico de los espesantes [71].

Se

y

necesitan

fascinante

ensayos

camino

controlados

para

desarrollar

deberemos abordar en el futuro. Por último, a pesar de su disponibilidad comercial, existe una gran controversia alrededor de la aplicación clínica de la e-stim transcutánea en la rehabilitación

de

la

deglución.

Uno

de

los

La tendencia actual, sin embargo, en el tratamiento

principales puntos de discusión se refiere a su

de la disfagia es ir un paso más allá y no quedarnos

aplicación

en la pura compensación del trastorno deglutorio,

establecimiento de una investigación exhaustiva

sino incidir en la recuperación de la función

que fundamente su aplicación basada en la

deglutoria. Los estudios realizados en esta Tesis

evidencia. Además, a pesar de ser una técnica que

Doctoral han representado el inicio de una nueva

podría tener un potencial de rehabilitación para

línea

grupo

algunos grupos de pacientes, en determinadas

fundamentada precisamente en este principio, en

condiciones, no implica que sea sinónimo de que

movernos de los tratamientos compensatorios a los

pueda

que promueven la recuperación. A pesar de que

universalmente eficaz para las alteraciones de la

pueden considerarse exploratorios, los estudios

deglución. Se necesitará pues, continuar evaluando

presentados nos han permitido sentar las bases

exhaustivamente

para el diseño de nuevos estudios aleatorizados

seguridad de la terapia en cada fenotipo en

controlados, que se están realizando actualmente

concreto de pacientes con disfagia, en estudios

en el grupo, con el objetivo de confirmar si los

clínicos futuros. Será también de interés resolver si

efectos fisiológicos evidenciados tienen impacto en

el efecto observado sobre la biomecánica de la

la evolución clínica de los pacientes y evaluar sus

deglución es consecuencia, al menos en parte, de

efectos a largo plazo.

un efecto neuromodulatorio que promocione la

de

investigación

en

nuestro

Los agonistas TRP (piperina, capsaicina) han mostrado efectos terapéuticos positivos, mejorando

clínica

ser

un

reorganización

generalizada

patrón

tanto

de

los

de

la

antes

del

rehabilitación

eficacia

circuitos

como

la

deglutorios

corticales.

diferentes parámetros deglutorios en pacientes con

Para

disfagia,

efectivos para la DO, es esencial la realización de

aunque

presentado

deben

los

estudios

considerarse

que

hemos

pruebas

de

continuar

estudios

- 151 -

diseñando

fisiopatológicos

tratamientos

y

más

neurofisiológicos

Discusión general________________________________________________________________ exhaustivos que nos permitan conocer cuáles son

aspecto

los actores implicados en el proceso deglutorio,

actualmente.

Sin

cómo

organizativos

y

interactúan,

cómo

se

alteran

en

la

totalmente

diferente embargo,

clínicos

al

que

aspectos

deberán

tiene éticos,

tenerse

en

enfermedad y a partir de aquí, cómo podemos

consideración a la hora de realizar la transición de

intervenir para prevenir o revertir ésta alteración. La

estas nuevas técnicas neuromoduladoras desde el

combinación de las técnicas actuales de estudio de

laboratorio de investigación a la rutina de la práctica

la función deglutoria como son la VFS y la

clínica.

manometría

faringoesofágica,

con

estudios

neurofisiológicos que nos permitan evaluar tanto la

Referencias

vía sensorical aferente, como la función de la corteza cerebral faríngea y la vía eferente, será fundamental

para

el

diseño

de

1.

World Health Organization. ICD-10 Version: 2010 [online]. 2010 [cited 13 April 2014]. Available from: http://apps.who.int/classifications/icd10/browse/ 2010/en#/R13

2.

Puisieux F, D'Andrea C, Baconnier P, Bui-Dinh D, Castaings-Pelet S, Crestani B, et al. Swallowing disorders, pneumonia and respiratory tract infectious disease in the elderly. Rev Mal Respir 2011;28: e76-93

futuras

intervenciones. En nuestro grupo estamos empezando a realizar los primeros estudios en este sentido mediante diferentes técnicas como son los potenciales sensoriales

evocados

faríngeos

(evaluados

mediante EEG) para el estudio de la vía aferente, y los

potenciales

motores

evocados

faríngeos

(evaluados mediante TMS) para el estudio de la vía eferente. Resultados provinentes de este tipo de estudios nos premitirán sentar las bases de nuevas estrategias terapéuticas centradas en mecanismos neuromoduladores y en la promoción de la plasticidad cortical. En resumen, las estrategias de neuro-estimulación, tanto las que hemos evaluado en esta Tesis Doctoral como otras estrategias de estimulación periférica

(estimulación

eléctrica

intrafaríngea),

estimulación central (rTMS, tDCS) o estimulación combinada (Paired associative stimulation) nos abren una nueva puerta en el tratamiento de la disfagia, que cambia el foco de la rehabilitación o compensación de la alteración biomecánica, para centrarse en los sistemas neuronales subyacentes (Ver Anexo 2). Si estas líneas de investigación confirman las buenas perspectivas mostradas en los estudios iniciales y consiguen mejorar el pronóstico clínico de los pacientes, probablemente el tratamiento de la disfagia en unos años tendrá un

- 152 -

3. Lieu PK, Chong MS, Seshadri R. The impact of swallowing disorders in the elderly. Ann Acad Med Singapore 2001;30:148-54. 4. Agencia de Evaluación de Tecnología e Investigación Médicas, Generalitat de Catalunya. Guía de Práctica Clínica del Ictus [online]. 2007 [cited 13 April 2014]. Available from: http://www.gencat.cat/salut/depsan/units/aatrm/ pdf/gp07ictuses.pdf 5. Abilleira S, Ribera A, Sanchez E, Tresserras R, Gallofre M. The Second Stroke Audit of Catalonia shows improvements in many, but not all quality indicators. Int J Stroke 2012;7:1924. 6. Ickenstein GW, Riecker A, Hohlig C, Muller R, Becker U, Reichmann H, et al. Pneumonia and in-hospital mortality in the context of neurogenic oropharyngeal dysphagia (NOD) in stroke and a new NOD step-wise concept. J Neurol 2010;257:1492-9. 7. Hinchey JA, Shephard T, Furie K, Smith D, Wang D, Tonn S. Formal dysphagia screening protocols prevent pneumonia. Stroke 2005;36:1972-6.

Discusión general

8. Bours GJ, Speyer R, Lemmens J, Limburg M, de WR. Bedside screening tests vs. videofluoroscopy or fibreoptic endoscopic evaluation of swallowing to detect dysphagia in patients with neurological disorders: systematic review. J Adv Nurs 2009;65:477-93. 9. Speyer R. Oropharyngeal dysphagia: screening and assessment. Otolaryngol Clin North Am 2013;46:989-1008.

effects. Ann Otol 2007;116:858-65.

Rhinol

Laryngol

18. Serra-Prat M, Hinojosa G, Lopez D, Juan M, Fabre E, Voss DS, et al. Prevalence of oropharyngeal dysphagia and impaired safety and efficacy of swallow in independently living older persons. J Am Geriatr Soc 2011;59:1867.

10. Belafsky PC, Mouadeb DA, Rees CJ, Pryor JC, Postma GN, Allen J, et al. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol 2008;117:919-24.

19. Cabre M, Serra-Prat M, Force L, Almirall J, Palomera E, Clave P. Oropharyngeal dysphagia is a risk factor for readmission for pneumonia in the very elderly persons: observational prospective study. J Gerontol A Biol Sci Med Sci 2014;69:330-7.

11. Martino R, Silver F, Teasell R, Bayley M, Nicholson G, Streiner DL, et al. The Toronto Bedside Swallowing Screening Test (TORBSST): development and validation of a dysphagia screening tool for patients with stroke. Stroke 2009;40:555-61.

20. Lee A, Sitoh YY, Lieu PK, Phua SY, Chin JJ. Swallowing impairment and feeding dependency in the hospitalised elderly. Ann Acad Med Singapore 1999;28:371-6.

12. Kertscher B, Speyer R, Palmieri M, Plant C. Bedside screening to detect oropharyngeal Dysphagia in patients with neurological disorders: an updated systematic review. Dysphagia 2014;29:204-12. 13. Leder SB, Suiter DM, Warner HL, Acton LM, Siegel MD. Safe initiation of oral diets in hospitalized patients based on passing a 3ounce (90 cc) water swallow challenge protocol. QJM 2012;105:257-63. 14. Leder SB, Suiter DM, Warner HL, Acton LM, Swainson BA. Success of recommending oral diets in acute stroke patients based on passing a 90-cc water swallow challenge protocol. Top Stroke Rehabil 2012;19:40-4. 15. Clave P, Arreola V, Romea M, Medina L, Palomera E, Serra-Prat M. Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration. Clin Nutr 2008;27:806-15. 16. Holland G, Jayasekeran V, Pendleton N, Horan M, Jones M, Hamdy S. Prevalence and symptom profiling of oropharyngeal dysphagia in a community dwelling of an elderly population: a self-reporting questionnaire survey. Dis Esophagus 2011;24:476-80. 17. Roy N, Stemple J, Merrill RM, Thomas L. Dysphagia in the elderly: preliminary evidence of prevalence, risk factors, and socioemotional

- 153 -

21. Cabre M, Serra-Prat M, Palomera E, Almirall J, Pallares R, Clave P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing 2010;39:39-45. 22. Kim TN, Choi KM. Sarcopenia: Definition, Epidemiology, and Pathophysiology. J Bone Metab 2013;20:1-10. 23. Ney DM, Weiss JM, Kind AJ, Robbins J. Senescent swallowing: impact, strategies, and interventions. Nutr Clin Pract 2009;24:395-413. 24. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-M156. 25. Clave P, de Kraa M, Arreola V, Girvent M, Farre R, Palomera E, et al. The effect of bolus viscosity on swallowing function in neurogenic dysphagia. Aliment Pharmacol Ther 2006;24:1385-94. 26. Kahrilas PJ, Lin S, Rademaker AW, Logemann JA. Impaired deglutitive airway protection: a videofluoroscopic analysis of severity and mechanism. Gastroenterology 1997;113:145764. 27. Rofes L, Arreola V, Almirall J, Cabre M, Campins L, Garcia-Peris P, et al. Diagnosis and management of oropharyngeal dysphagia and its nutritional and respiratory complications in the elderly. Gastroenterol Res Pract [serial on the internet]. 2011[cited 13 April 2014];

Discusión general________________________________________________________________ 2011. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2 929516/ 28. van der Maarel-Wierink CD, Vanobbergen JN, Bronkhorst EM, Schols JM, de BC. Metaanalysis of dysphagia and aspiration pneumonia in frail elders. J Dent Res 2011;90:1398-404. 29. van der Maarel-Wierink CD, Vanobbergen JN, Bronkhorst EM, Schols JM, de BC. Risk factors for aspiration pneumonia in frail older people: a systematic literature review. J Am Med Dir Assoc 2011;12:344-54. 30. Marik PE. Aspiration pneumonitis aspiration pneumonia. N Engl J 2001;344:665-71.

and Med

31. Committee for the Japanese Respiratory Society Guidelines in Management of Respiratory Infections. Aspiration pneumonia. Respirology 2004;9 Suppl 1:S35-S37. 32. Loeb M, Neupane B, Walter SD, Hanning R, Carusone SC, Lewis D, et al. Environmental risk factors for community-acquired pneumonia hospitalization in older adults. J Am Geriatr Soc 2009;57:1036-40. 33. Riquelme R, Torres A, El-Ebiary M, de la Bellacasa JP, Estruch R, Mensa J, et al. Community-acquired pneumonia in the elderly: A multivariate analysis of risk and prognostic factors. Am J Respir Crit Care Med 1996;154:1450-5. 34. Marik PE, Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest 2003;124:32836. 35. Fernandez-Sabe N, Carratala J, Roson B, Dorca J, Verdaguer R, Manresa F, et al. Community-acquired pneumonia in very elderly patients: causative organisms, clinical characteristics, and outcomes. Medicine (Baltimore) 2003;82:159-69. 36. Teramoto S, Fukuchi Y, Sasaki H, Sato K, Sekizawa K, Matsuse T. High incidence of aspiration pneumonia in community- and hospital-acquired pneumonia in hospitalized patients: a multicenter, prospective study in Japan. J Am Geriatr Soc 2008;56:577-9. 37. Serra-Prat M, Palomera M, Gomez C, SarShalom D, Saiz A, Montoya JG, et al.

- 154 -

Oropharyngeal dysphagia as a risk factor for malnutrition and lower respiratory tract infection in independently living older persons: a population-based prospective study. Age Ageing 2012;41:376-81. 38. Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-63. 39. Katzan IL, Cebul RD, Husak SH, Dawson NV, Baker DW. The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003;60:620-5. 40. Speyer R, Baijens L, Heijnen M, Zwijnenberg I. Effects of therapy in oropharyngeal dysphagia by speech and language therapists: a systematic review. Dysphagia 2010;25:40-65. 41. Geeganage C, Beavan J, Ellender S, Bath PM. Interventions for dysphagia and nutritional support in acute and subacute stroke. Cochrane Database Syst Rev 2012;10:CD000323. 42. Bhattacharyya N, Kotz T, Shapiro J. The effect of bolus consistency on dysphagia in unilateral vocal cord paralysis. Otolaryngol Head Neck Surg 2003;129:632-6. 43. Groher M. Bolus management and aspiration pneumonia in patients with pseudobulbar dysphagia. Dysphagia 1987;1:215-6. 44. Cichero JA, Steele C, Duivestein J, Clave P, Chen J, Kayashita J, et al. The Need for International Terminology and Definitions for Texture-Modified Foods and Thickened Liquids Used in Dysphagia Management: Foundations of a Global Initiative. Curr Phys Med Rehabil Reports 2013;1:280-91. 45. Shim JS, Oh BM, Han TR. Factors associated with compliance with viscosity-modified diet among dysphagic patients. Ann Rehabil Med 2013;37:628-32. 46. Dantas RO, Kern MK, Massey BT, Dodds WJ, Kahrilas PJ, Brasseur JG, et al. Effect of swallowed bolus variables on oral and pharyngeal phases of swallowing. Am J Physiol 1990;258:G675-G681. 47. Gallas S, Marie JP, Leroi AM, Verin E. Sensory transcutaneous electrical stimulation improves

Discusión general

post-stroke dysphagic patients. Dysphagia 2010;25:291-7. 48. Jayasekeran V, Singh S, Tyrrell P, Michou E, Jefferson S, Mistry S, et al. Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions. Gastroenterology 2010;138:1737-46. 49. McNamara FN, Randall A, Gunthorpe MJ. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol 2005;144:781-90. 50. Alvarez-Berdugo D, Jimenez M, Clave P, Rofes L. Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells. Scientific World Journal [serial on the internet]. 2014[cited 13 April 2014];2014: Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3 929291/ 51. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998;21:53143. 52. Logemann JA, Pauloski BR, Colangelo L, Lazarus C, Fujiu M, Kahrilas PJ. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res 1995;38:55663. 53. Pelletier CA, Dhanaraj GE. The effect of taste and palatability on lingual swallowing pressure. Dysphagia 2006;21:121-8. 54. Hill RJ, Dodrill P, Bluck LJ, Davies PS. A novel stable isotope approach for determining the impact of thickening agents on water absorption. Dysphagia 2010;25:1-5. 55. Sharpe K, Ward L, Cichero J, Sopade P, Halley P. Thickened fluids and water absorption in rats and humans. Dysphagia 2007;22:193-203. 56. McGrail A, Kelchner LN. Adequate oral fluid intake in hospitalized stroke patients: does viscosity matter? Rehabil Nurs 2012;37:252-7. 57. Cichero JA. Thickening agents used for dysphagia management: effect on bioavailability of water, medication and feelings of satiety. Nutr J 2013;12:54.

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58. U.S.Food and Drug Administration. The Biopharmaceutics Classification System (BCS) Guidance [online]. 2009 [cited 13 April 2014]. Available from: http://www.fda.gov/AboutFDA/CentersOffices/O fficeofMedicalProductsandTobacco/CDER/ucm 128219.htm 59. Canadian Centre for Occupational Health and Safety, International Programme on Chemical Safety. Xanthan gum [online]. 2014 [cited 13 April 2014]. Available from: http://www.inchem.org/documents/jecfa/jecmon o/v21je13.htm 60. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. Int J Toxicol 2007;26 Suppl 1:3-106. 61. Hicks GA. TRP channels as therapeutic targets: hot property, or time to cool down? Neurogastroenterol Motil 2006;18:590-4. 62. U.S.Food and Drug Administration. Generally Recognized as Safe (GRAS) [online]. 2014 [cited 13 April 2014]. Available from: http://www.fda.gov/food/ingredientspackagingla beling/gras/default.htm 63. Myers BM, Smith JL, Graham DY. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol 1987;82:211-4. 64. Koleva II, van Beek TA, Soffers AE, Dusemund B, Rietjens IM. Alkaloids in the human food chain--natural occurrence and possible adverse effects. Mol Nutr Food Res 2012;56:30-52. 65. US Food and Drug Administration. FDA VitalStim clearance letter [online]. 2002 [cited 13 April 2014]. Available from: http://www.vitalstim.com/uploadedFiles/Health_ Professionals/FDA_VitalStim_clearance_letter. pdf 66. National Institute for Health and Care Excellence. Interventional procedure overview of transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia [online]. 2014 [cited 13 April 2014]. Available from: http://www.nice.org.uk/nicemedia/live/14068/66 167/66167.pdf

Discusión general________________________________________________________________ 67. National Institute for Health and Care Excellence. Transcutaneous Neuromuscular Electrical Stimulation (NMES) for oropharyngeal dysphagia [online]. 2014 [cited 13 April 2014]. Available from: http://guidance.nice.org.uk/IP/1033 68. Baijens LW, Speyer R. Effects of therapy for dysphagia in Parkinson's disease: systematic review. Dysphagia 2009;24:91-102. 69. Ashford J, McCabe D, Wheeler-Hegland K, Frymark T, Mullen R, Musson N, et al. Evidence-based systematic review: Oropharyngeal dysphagia behavioral

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treatments. Part III--impact of dysphagia treatments on populations with neurological disorders. J Rehabil Res Dev 2009;46:195-204. 70. Matta Z, Chambers E, Mertz GJ, McGowan Helverson JM. Sensory characteristics of beverages prepared with commercial thickeners used for dysphagia diets. J Am Diet Assoc 2006;106:1049-54. 71. Low J, Wyles C, Wilkinson T, Sainsbury R. The effect of compliance on clinical outcomes for patients with dysphagia on videofluoroscopy. Dysphagia 2001;16:123-7.

CONCLUSIONES

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Conclusiones

CONCLUSIONES 1. El método de cribado EAT-10 y el método MECV-V de evaluación clínica para la DO presentan una alta sensibilidad y especificidad para detectar a los

pacientes con disfagia orofaríngea y

alteraciones deglutorias y para identificar aquellos pacientes que necesitarán una prueba instrumental o una evaluación clínica más exhaustiva. 2. El anciano frágil y el anciano con neumonía adquirida en la comunidad presentan una elevada prevalencia de signos videofluorscópicos de alteración de la eficacia y de la seguridad de la deglución. El retraso en el tiempo del cierre del vestíbulo laríngeo y en el movimiento vertical del hioides son los factores críticos que determinan la presencia de alteraciones de seguridad (penetraciones y aspiraciones) mientras que la débil fuerza de propulsión del bolo alimentario es el factor crítico que nos determina la presencia de alteraciones de la eficacia (residuo orofaríngeo). 3. La disfagia orofaríngea es un factor de riesgo para la neumonía adquirida en la comunidad en el anciano que no suele ser identificado como tal en la práctica clínica. 4. La disfagia orofaríngea es un factor de mal pronóstico clínico en el anciano frágil y en el anciano con neumonía adquirida en la comunidad, asociándose a unos altos índices de mortalidad. 5. Los espesantes de goma xantana mejoran la seguridad de la deglución de forma concentracióndependiente, sin aumentar el residuo orofaríngeo y sin modificar la respuesta motora orofaríngea. A viscosidad néctar, el efecto terapéutico depende exclusivamente de las características intrínsecas del bolo. A viscosidad pudin, se añade un efecto causado por la disminución de la velocidad del bolo por la faringe. 6. A pesar de que nuestros estudios sugieren una ventaja terapeútica, son necesarios estudios comparativos para confirmar que los espesantes de goma xantana muestran un perfil terapéutico superior a los espesantes de almidón modificado, tanto a nivel videofluoroscópico como a nivel de cumplimiento terapéutico. 7. La suplementación del bolo alimentario con agonistas de los canales TRP (capsaicina y piperina) acorta el tiempo de cierre del vestíbulo laríngeo reduciendo así las penetraciones al vestíbulo laríngeo y aspiracioneos traqueo-bronquiales. La capsaicina, a diferencia de la piperina, también mejora la eficacia de la deglución, reduciendo la prevalencia de residuo orofaríngeo. 8. Nuestros estudios sugieren que los canales TRP son una diana farmacológica interesante para el tratamiento de la DO, pero se deberán explorar los efectos a largo plazo de los agonistas de estos receptores, así como sus efectos a nivel neuro-fisiológico. 9. La estimulación eléctrica transcutánea es un tratamiento seguro y eficaz para la DO crónica después de un ictus. La estimulación eléctrica transcutánea aplicada a intensidad sensorial, acorta el tiempo de cierre del vestíbulo laríngeo, reduciendo las alteraciones de la seguridad de la deglución, mientras que aplicada a intensidad motora sobre la musculatura supra-hioidea también mejora la eficacia de la deglución reduciendo el residuo orofaríngeo.

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ANEXO 1

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ANEXO 2

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Fisiopatologia, diagnòstic i noves estratègies terapèutiques - Dialnet

Fisiopatologia, diagnòstic i noves estratègies terapèutiques per a la disfàgia orofaríngia neurògena o associada a l’envelliment Tesi doctoral present...

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