Dysphagia Following Endotracheal Intubation: Frequency, Risk Factors And

Dysphagia Following Endotracheal Intubation: Frequency, Risk Factors and

Characteristics

Stacey Anne Skoretz

A thesis submitted in conformity

with the requirements

for the degree of Doctor of Philosophy

Department of Speech-Language Pathology

University of Toronto

DYSPHAGIA FOLLOWING INTUBATION

Dysphagia Following Endotracheal Intubation: Frequency, Risk Factors and

Characteristics

Stacey Anne Skoretz

Doctor of Philosophy

Department of Speech Language Pathology University of Toronto

2015

Abstract

Oropharyngeal dysphagia following endotracheal intubation occurs frequently, however, both the incidence and associated risk factors vary across the literature. This dissertation is comprised of three studies that investigate the frequency, associated risk factors and characteristics of post-extubation dysphagia along with the relation between intubation duration and swallowing outcomes with a focus on CV surgery. First, we conducted a systematic review in order to determine dysphagia frequency according to patient diagnoses and the association between dysphagia and intubation time. We conducted searches using fourteen electronic databases along with manual searching of journals and grey literature. Our critical appraisal utilized the Cochrane Risk of Bias

Assessment and GRADE tools. Our second study assessed dysphagia frequencies according to four intubation duration strata on consecutive patients following CV surgery: I (≤12 h), II (>12 to ≤24 h), III (> 24 to ≤ 48 h), and IV (>48 h). We also derived independent predictors for dysphagia across the entire sample using logistic regression. Finally, we conducted a feasibility study with prospective consecutive enrollment in order to determine patient tolerance of the instrumental procedures used to assess swallowing physiology, videofluoroscopy swallowing study (VFS) and

ii DYSPHAGIA FOLLOWING INTUBATION nasendoscopy, following prolonged intubation after CV surgery. Along with study impact on patients and nursing workflow, we assessed other feasibility parameters including recruitment rate, task completion durations and measurement reliability.

Findings from our systematic review, identified a range of dysphagia frequency from 3% to 62% and intubation duration from 124.8 to 346.6 mean hours across the fourteen included studies. The highest dysphagia frequencies, 62%, 56%, and 51%, occurred following prolonged intubation and included patients across all diagnostic subtypes.

Overall, the quality of the evidence was low. In our second study, we reported a dysphagia frequency of 5.6 % (51/909) across the entire sample, however, we identified that frequency varied according to intubation group: I, 1 % (7/699); II, 8.2 % (11/134);

III, 16.7 % (6/36); and IV, 67.5 % (27/40). Across the entire sample, the independent predictors of dysphagia included intubation duration (p < .001; odds ratio [OR] 1.93,

95 % confidence interval [CI] 1.63-2.29) according to 12-hour increments and age (p =

.004; OR 2.12, 95 % CI 1.27-3.52) according to 10-year increments. For our final study, of the 16 eligible patients, three agreed to participate. Following a videofluoroscopy swallowing study (VFS) completion, all patients exhibited oral and pharyngeal swallowing impairments. VFS completion time ranged from 14 to 52 minutes with item interrater reliability ranging from .25 (95% CI: -.10-.59) to .99 (95% CI: .98-.99).

Participants reported minimal study burden. In conclusion, our collective findings report the frequency of dysphagia across numerous patient populations, associated risk factors and swallowing characteristics. With this information, we provide the means to identify at-risk patients following extubation after CV surgery. For future studies, we propose ways to improve study enrollment as well as suggest instrumental procedures and

iii DYSPHAGIA FOLLOWING INTUBATION interpretation methods best suited to assessing swallowing physiology in this patient population.

iv DYSPHAGIA FOLLOWING INTUBATION

Acknowledgements

It takes a village. No kidding. I am the luckiest human on the planet to have a community such as this. If it were not for the selfless acts of kindness, love and support that I received; I would have never finished this marathon. The people I am about to mention were my supports when I could not stand on my own, my foundation when everything around me was turning to sand, and my light when all I could see was dark.

What you all have done throughout this process will never be lost on me.

For my husband Bill: thank you for sacrificing so much throughout these years and especially during the final three as we struggled to survive, quite literally. You have provided for our little family, taken on the role of primary caregiver more times than I can count, and taken countless hours off of work to provide support without ever uttering one word of complaint. Your capacity for love, tolerance and understanding is remarkable. To my baby Grace: thank you for being such a Life Force. You always greet the day happily and readily embrace it with vigor - there is nothing that is more perfect than that. Thank you for adding a dimension to my life that I would not have otherwise had. I do apologize that the first words you heard and books you read were all surrounding deglutition. I’ve started putting away for your future therapy.

To my supervisor Dr. Rosemary Martino: I thank you mightily for your guidance, knowledge, support, sacrifice and confidence you have in my work and in me. While what you offer the profession is remarkable, it is second only to your kindness, integrity and humanity. For my supervisory committee Drs. Joan Ivanov, John Granton and

Terrence Yau: thank you for your expertise, patience and support. I am honoured that you agreed to mentor me throughout this journey. I strive for your balance of research and clinical practice. For the Ladies-of-the-Lab: Trixie Reichardt, Dr. Heather Flowers

v DYSPHAGIA FOLLOWING INTUBATION

and Stephanie Shaw, thank you for playing such an important role in my successes both

personally and professionally. I am so happy that you are a part of my life.

Thank you for everything you have done for me Mom. I have not forgotten the life sacrifices you have made to get me here. Without the past, there would be no present. To my sister Cassandra, I will never forget the help you provided while we were renovation refugees and while I was in the newborn baby haze. To my sister Mikaela: this adventure would have been a lot less Awesome without you. From saving all your high-school pennies to come visit Toronto to your presence during the important events of this journey, thank you for being there. Someday I really will find you a “solar- powered laser beam guitar”. For my aunt Hélène: thank you for understanding me. The generosity and empathy you possess is without measure. I quite literally would not have survived without you.

Michelle Graham, thank you for being my steadfast friend throughout these years.

Above all, you were the only person who was there by my side as I packed up my life’s rubble to start another. Thank you. Vance Ward, you supported this adventure not only with your time and friendship but also with your remarkable culinary skills. Thank you for feeding my stomach and my soul. To my dear Kelly Ryan, David Rose and the rest of the Hamilton/Grimsby gang: who wouldn’t want to have a Ph.D. with a minor in viniculture? I will now have time to become learned in the ways of that “Rock Lobster” thing and I have not forgotten that our off-grid life adventures wait. For Mar and Shar: I am so grateful that our paths collided and blessed me with you, Mar-toonies and harp strings. You have added depth and fuel for my right hemisphere. For Drs. Jim Coyle and

Joe Murray: thank you for checking in over the years and making sure that I was still

vi DYSPHAGIA FOLLOWING INTUBATION alive. Your help and balanced wisdom really did keep things on track. For Randy

Reichardt and Megan Sui: I am eternally grateful for your mad library skills.

Lastly but certainly not least, to Dr. John Stone: without you this would have never came to be. Thank you for giving me my very first research assistantship during my master’s and encouraging me to pursue doctoral studies. You helped me to believe that I was capable and had skills worthy of higher learning. Without that and all of the kind gestures you and your wonderful wife Sandra have displayed over the years, I would not have made it to this point. Thank you for being a role model for me in this world of academia. Your intellect, candor, practicality and humour are something that I respect deeply. You have shown me that there is much to be gained and to offer throughout this process. I can only hope to have even a fraction of that same positive impact on this

Earth.

Onward…

vii DYSPHAGIA FOLLOWING INTUBATION

TABLE OF CONTENTS

Abstract ...... ii Acknowledgements ...... v Table of Contents ...... viii List of Tables ...... xii List of Figures ...... xiii List of Appendices ...... xiv List of Abbreviations ...... xv

INTRODUCTION

1. Chapter I ...... 1 I. The Swallow ...... 2 Normal Swallowing Physiology ...... 2 Swallowing Stages ...... 2 The vagus nerve ...... 5 Airway protection during the swallow ...... 6 Respiration and swallowing ...... 7 Aging ...... 9 Diagnosing Dysphagia ...... 10 Dysphagia Screening ...... 10 Clinical Swallowing Evaluation ...... 13 Instrumental Swallowing Assessments ...... 15 The videofluoroscopic swallow study ...... 16 Fiberoptic endoscopic evaluation of the swallow ...... 20 Fiberoptic endoscopic evaluation of the swallow with sensory testing ... 21 VFS versus FEES: Which to choose? ...... 22 II. Endotracheal Intubation and Mechanical Ventilation ...... 24 Background ...... 24 Dysphagia Following Endotracheal Intubation ...... 24 Dysphagia characteristics ...... 28 Consequences of dysphagia ...... 29 Etiology of Post-extubation Dysphagia ...... 32 Endotracheal Intubation ...... 32 Upper aerodigestive tract morbidities ...... 33 Injury and biomechanical changes ...... 33 Injury etiology ...... 35 Mechanical Ventilation and the Swallow ...... 36 Breathing and swallowing: Taxing an already taxed system ...... 37 Anesthesia and Upper Aerodigestive Function ...... 39 III. Cardiovascular Surgery ...... 42 Heart Disease ...... 42 Burden of Care ...... 42 Heart Disease Risk Factors ...... 42 Cardiovascular Surgery Types ...... 43 Risk Factors for Dysphagia Following CV Surgery ...... 45

viii DYSPHAGIA FOLLOWING INTUBATION

Surgery Type ...... 46 Transesophageal Echocardiogram ...... 46 Cardiopulmonary Bypass ...... 48 Stroke ...... 49 Recurrent Laryngeal Nerve Injury ...... 49 Prolonged Intubation Following Cardiovascular Surgery ...... 51 Age ...... 53 Dysphagia Characteristics ...... 54 Gaps in the Literature ...... 55 Purposes ...... 57

THE INCIDENCE OF DYSPHAGIA FOLLOWING ENDOTRACHEAL INTUBATION: A SYSTEMATIC REVIEW

2. Chapter II ...... 59 Abstract ...... 59 Introduction ...... 61 Materials and Methods ...... 63 Operational Definitions ...... 63 Search Strategy ...... 63 Eligibility Criteria ...... 64 Study Selection ...... 64 Assessment of Methodological Quality ...... 64 Data Extraction ...... 65 Results ...... 66 Literature Retrieved ...... 66 Study Characteristics and Quality Assessment ...... 69 Dysphagia Following Endotracheal Intubation ...... 73 Duration of Intubation and the Frequency Dysphagia ...... 73 Swallowing Assessment Methods ...... 74 Frequency of Dysphagia Following Intubation ...... 75 Discussion ...... 79

DYSPHAGIA AND ASSOCIATED RISK FACTORS FOLLOWING EXTUBATION IN CARDIOVASCULAR SURGICAL PATIENTS

3. Chapter III ...... 83 Abstract ...... 83 Introduction ...... 85 Patients and Methods ...... 86 Data Abstraction ...... 86 Operational Definitions ...... 87 Statistical Analyses ...... 87 Results ...... 88 Dysphagia Frequency and Criteria ...... 89 Intubation Duration Across Study Sample ...... 90

ix DYSPHAGIA FOLLOWING INTUBATION

Patient Characteristics Across Study Sample ...... 90 Discussion ...... 100

DYSPHAGIA INCIDENCE AND SWALLOWING PHYSIOLOGY FOLLOWING PROLONGED INTUBATION AFTER CARDIOVASCULAR SURGERY: A FEASIBILITY STUDY

4. Chapter IV ...... 104 Abstract ...... 104 Introduction ...... 106 Methods ...... 109 Participants ...... 109 Study Process ...... 109 Videofluoroscopic Swallow Study ...... 110 Imaging ...... 110 Videofluoroscopic Swallow Study Procedure ...... 110 Videofluoroscopic Swallow Study Measures ...... 111 Standardized VFS Assessment Tools ...... 111 Displacement Measurements ...... 113 Study Impact Questionnaires and Patient Variables ...... 114 Scoring and Statistical Analyses ...... 117 Results ...... 118 Patient Recruitment and Characteristics ...... 118 Videofluoroscopic Swallow Study ...... 120 Videofluoroscopic Measures ...... 121 Standardized VFS assessment tools ...... 122 Displacement measurements ...... 125 Study Impact Questionnaires ...... 127 Patient Comfort Questionnaire ...... 127 Workload Impact Questionnaires ...... 127 Discussion ...... 128

DISCUSSION

5. Chapter V ...... 137 Introduction ...... 137 Summary of Thesis Findings ...... 138 Clinical Implications ...... 144 Research Implications ...... 146 Future Studies ...... 148 Limitation of the Thesis ...... 151 Conclusions ...... 152

x DYSPHAGIA FOLLOWING INTUBATION

REFERENCES

6. References ...... 155

APPENDICES

7. Appendices ...... 225

xi DYSPHAGIA FOLLOWING INTUBATION

LIST OF TABLES

Table 1.1. Description and critical appraisal of screening tools used with patients following extubation ...... 12 Table 2.1. Study characteristics and frequency of dysphagia according to patient diagnosis ...... 70 Table 2.2. Risk of bias and methodological quality (GRADE) across studies ...... 72 Table 2.3. Intubation duration according to presence of dysphagia ...... 74 Table 2.4a. Surgical and medical risk factor association with dysphagia ...... 77 Table 2.4b. Studies either supporting or not supporting risks for dysphagia ...... 78 Table 3.1. Comparing dysphagia frequency and intubation duration across intubation groups ...... 90 Table 3.2. Pre-operative demographics and presenting clinical characteristics across sample ...... 92 Table 3.3. Peri-operative characteristics across sample ...... 95 Table 3.4. Post-operative patient outcomes across sample ...... 97 Table 3.5. Independent predictors of postoperative dysphagia ...... 99 Table 4.1. MBSImpTM© oral and pharyngeal components ...... 112 Table 4.2. Penetration-Aspiration Scale ...... 113 Table 4.3. Survey questions ...... 116 Table 4.4. Patient characteristics ...... 120 Table 4.5. Task completion time and interrater reliability according to VFS measure . 122 Table 4.6. Hyoid displacement measurements according to patient ...... 126

xii DYSPHAGIA FOLLOWING INTUBATION

LIST OF FIGURES

Figure 2.1. Study selection process ...... 68 Figure 4.1. Study enrollment ...... 119 Figure 4.2a. MBSImpTM© oral components across patients ...... 123 Figure 4.2b. MBSImpTM© pharyngeal components across patients ...... 124 Figure 4.3. Pharyngeal constriction ratio by patient according to bolus texture and volume ...... 127

xiii DYSPHAGIA FOLLOWING INTUBATION

LIST OF APPENDICES

Appendix A – CHEST Licenses ...... 225 Appendix B – Systematic Review Proposal ...... 237 Appendix C – Study Selection Form ...... 240 Appendix D – Cochrane Collaboration’s Risk of Bias Assessment ...... 241 Appendix E – Data Extraction Form ...... 242 Appendix F – Explanatory Meta-Analyses ...... 243 Appendix G – Search Strategies Across Databases ...... 247 Appendix H – Non-English Articles ...... 248 Appendix I – Handsearched Journals and Reference Yield ...... 249 Appendix J – Dysphagia Licenses ...... 250 Appendix K – Data Abstraction Manual ...... 254 Appendix L – Medical Record Review Form ...... 258 Appendix M – Retrospective Study Sample Size Estimation ...... 260 Appendix N – Characteristics of Intubation Stratum I ...... 261 Appendix O – Characteristics of Intubation Stratum II ...... 265 Appendix P – Characteristics of Intubation Stratum III ...... 269 Appendix Q – Characteristics of Intubation Stratum IV ...... 273

xiv DYSPHAGIA FOLLOWING INTUBATION

LIST OF ABBREVIATIONS

APACHE Acute Physiology and Chronic Health Evaluation ASHA American Speech-Language and Hearing Association CABG Coronary artery bypass grafting CI Confidence interval CN Cranial nerve COPD Chronic Obstructive Pulmonary Disease CPAP Continuous positive airway pressure CPB Cardiopulmonary bypass CSE Clinical swallow evaluation CV Cardiovascular CVA Cerebral vascular accident DREP Dysphagia Risk Evaluation Protocol ETT Endotracheal tube FEES Fiberoptic Endoscopic Evaluation of the Swallow FEESST Fiberoptic Endoscopic Evaluation of the Swallow with Sensory Testing GBP Pound sterling GCS Glasgow Coma Score GERD Gastro-esophageal reflux disease GI Gastrointestinal GRADE Grading of Recommendation, Assessment, Development, and Evaluation hrs Hours IABP Intra-aortic balloon pump ICC Intraclass correlation coefficient ICU Intensive care unit inSLN Internal branch of the superior laryngeal nerve IQR Interquartile range LAR Laryngeal adductor response LCR Laryngeal cough reflex LOS Length of stay LP Laryngopharyngeal LV Left ventricular MBSImpTM© Modified Barium Swallow Measurement Tool for Swallow Impairment Profile MBS Modified barium swallow MI Myocardial infarction min Minute N/A Not applicable NG/NGT Nasogastric feeding tube NPO Nil per os NT Not tested NYHA New York Heart Association OI Overall impairment PA Pharyngeal area

xv DYSPHAGIA FOLLOWING INTUBATION

PAS Penetration Aspiration Scale PEG Percutaneous endoscopic gastronomy tube PMV Prolonged mechanical ventilation PC Pressure control PCR Pharyngeal constriction ratio PS Pressure support PV Pressure ventilation RLN Recurrent laryngeal nerve SD Standard deviation SLP Speech-language pathologist TEE Transesophageal echocardiography TIA Transient ischemic attack TWH Toronto Western Hospital US United States of America USD United States dollar VF Videofluoroscopic VFS Videofluoroscopic swallow study yrs Years

xvi

CHAPTER I

INTRODUCTION

Swallowing is a physiological act necessary for species viability. Swallowing food and/or fluid is often taken for granted until it is rendered dysfunctional. In the words of George Bernard Shaw: “there is no love sincerer than the love of food” (Shaw,

1903/2012, Act I, p. 74).

Oropharyngeal dysphagia, herein referred to as dysphagia, is an upper aerodigestive tract abnormality secondary to impaired swallowing physiology (Martino et al., 2005). It impairs one’s ability to safely engage in deglutition thereby leading to potential malnutrition (Smithard, O'Neill, Parks, & Morris, 1996; Westergren, Ohlsson,

& Rahm Hallberg, 2001), respiratory complications (Cabré et al., 2014; Kwok, Davis,

Cagle, Sue, & Kaups, 2013; Martino et al., 2005) and even death (Cabré et al., 2010;

Macht et al., 2011). In the United States (US) during 2004 and 2005, dysphagia prevalence in the acute care setting was estimated at 0.4% of all hospitalizations (Altman,

Yu, & Schaefer, 2010) and in those following mechanical ventilation, an incidence as high as 84% (Macht et al., 2011). The disorder is an economic burden leading to $547 million annually in additional hospitalization costs in the US alone (Altman et al., 2010;

Cichero & Altman, 2012). Post-extubation dysphagia also contributes to increased pneumonia, reintubation, and mortality (Macht et al., 2011). Those patients with dysphagia following extubation incur triple the healthcare costs as compared to those without (Ferraris, Ferraris, Moritz, & Welch, 2001).

This introductory chapter will provide background information for the research studies that follow, which focus on dysphagia following endotracheal intubation in general and following cardiovascular surgery more specifically. It is comprised of three

INTRODUCTION 2 major sections: I. The Swallow; II. Endotracheal Intubation and Mechanical Ventilation; and III. Cardiovascular (CV) Surgery. Together these sections review: normal swallow physiology and the current methods available by which to assess it; how the swallow may be impacted by endotracheal intubation, mechanical ventilation, and anesthesia in general; and finally how the swallow may be impacted in the CV surgical population.

I. The Swallow

Normal Swallowing Physiology

Swallowing stages. The swallow is a complex process involving 30 muscles located throughout the oral cavity, larynx and pharynx which are controlled by six cranial nerves (CN V, VII, IX-XII), three cervical nerve roots (C1-C3) and multiple cortical, subcortical and brainstem regions (Miller, Bieger, & Conklin, 1997; Shaw & Martino,

2013). Traditionally, the entire swallowing act was considered involuntary or reflexive and mitigated primarily through the infratenorium via a central pattern generator housed within the medulla oblongata (Miller, Bieger, & Conklin, 1997; Shaw & Martino, 2013).

With the advancement of imaging technologies it is now accepted that aspects of the swallow are governed by either the supratentorium or the infratentorium (Hamdy, Aziz,

Thompson, & Rothwell, 2001; Hamdy et al., 1999; Martin, Goodyear, Gati, & Menon,

2001; Michou et al., 2014; Shaw & Martino, 2013).

The act of swallowing is a continuous and dynamic sequence of events, which integrates the movement of multiple muscles and structures (Perlman & Christensen,

1997; Shaw & Martino, 2013). For descriptive purposes, it is traditionally divided into discrete stages: oral, pharyngeal and esophageal (Perlman & Christensen, 1997). The oral stage is further sub-divided into two phases: the oral preparatory and oral transport phases (Perlman & Christensen, 1997). These oral phases are primarily under volitional

INTRODUCTION 3

or supratentorial control (Hamdy et al., 1999; Humbert & Robbins, 2007; Martin,

Goodyear, Gati, & Menon, 2001; Palmer, Hiiemae, Matsuo, & Haishima, 2007), whereas

the pharyngeal and esophageal stages are considered reflexive or involuntary and

governed by the infratentorium (Diamant, 1995; Diamant, 1996; Ertekin, 2011; Ertekin &

Aydogdu, 2003; Michou et al., 2014; Miller, 1982; Miller, 1993). Historically, only

volitional swallowing events were considered modifiable (Hamdy et al., 1999; Humbert

& Robbins, 2007; Martin, Goodyear, Gati, & Menon, 2001; Palmer, Hiiemae, Matsuo, &

Haishima, 2007). Now, there is emerging evidence that those swallowing acts governed

by the infratentorium, once considered purely reflexive, may too be altered (Michou et

al., 2014). While their event sequence may not be modifiable, the response amplitude

and timing may be altered through intervention (Michou et al., 2014).

During the oral preparatory phase, the bolus is navigated throughout the oral

cavity onto the dental surfaces and throughout the lateral cheek sulci as needed (Palmer et

al., 2007; Palmer, Rudin, Lara, & Crompton, 1992). Once bolus preparation is complete,

the intrinsic tongue muscles create a trough-like furrow in order to contain the bolus between the dorsal tongue surface and hard palate readying the bolus for transport into the oropharynx (Cook et al., 1989; Curtis, Cruess, & Dachman, 1985; Dodds, Stewart, &

Logemann, 1990; Dodds et al., 1989; Taniguchi, Tsukada, Ootaki, Yamada, & Inoue,

2008). The pressure within the oropharynx increases with the tongue creating wave-like

movements transporting the bolus from the oral cavity posteriorly into the pharynx (Cook

et al., 1989; Curtis et al., 1985; Dantas et al., 1990; Dodds et al., 1989; McConnel, 1988;

Santander, Engelke, Olthoff, & Völter, 2013; Taniguchi et al., 2008).

The purpose of the pharyngeal stage, lasting approximately one second, is to move the bolus towards the upper esophageal sphincter (Cassiani, Santos, Parreira, &

INTRODUCTION 4

Dantas, 2011; Cook et al., 1989; Curtis, Cruess, Dachman, & Maso, 1984; Kahrilas,

1993; Logemann et al., 2000; Logemann, Pauloski, Rademaker, & Kahrilas, 2002;

McConnel, 1988). It is initiated with the depression of the posterior tongue and the

closure or the continued closure of multiple “valves” or “ports” throughout the upper

aerodigestive tract (Curtis et al., 1985; Olthoff, Zhang, Schweizer, & Frahm, 2014;

Shaker, Dodds, Dantas, Hogan, & Arndorfer, 1990). The resultant increased pressure, sequential tongue movements along with the initiation of a sphincter-like motion of the lateral and posterior pharyngeal walls assist with posterior bolus movement (Curtis et al.,

1985; Ekberg & Nylander, 1982; Kahrilas, Logemann, Lin, & Ergun, 1992; McConnel,

1988; Olthoff et al., 2014; Palmer, Tanaka, & Ensrud, 2000). The upper esophageal sphincter begins to relax (Jacob, Kahrilas, Logemann, Shah, & Ha, 1989) while the hyolaryngeal complex, which includes the hyoid bone and larynx, begin an anterior and superior ascent (Cook et al., 1989; Curtis et al., 1985; Logemann et al., 1992; Logemann et al., 2000; Logemann et al., 2002; Olthoff et al., 2014). As the true and false vocal folds close, the epiglottis begins to retroflex passively while covering the adducted arytenoid cartilages (Curtis et al., 1985; Ekberg & Sigurjónsson, 1982; Inamoto et al.,

2013; Logemann et al., 1992; Ohmae, Logemann, Kaiser, Hanson, & Kahrilas, 1995;

Shaker et al., 1990). At this time, an obligatory apneic period commences which typically lasts less than one second (Martin, Logemann, Shaker, Dodds, & Trammell,

1994; Martin-Harris, Brodsky, et al., 2005; Martin-Harris, Brodsky, Price, Michel, &

Walters, 2003; Selley, Flack, Ellis, & Brooks, 1989a). As the bolus begins its descent through the UES, the esophageal stage commences and lasts between 8 and 13 seconds

(De Vincentis et al., 1984). Esophageal peristalsis moves the bolus through the distal and proximal areas of the esophagus, through the lower esophageal sphincter and into the

INTRODUCTION 5 stomach (Goyal & Chaudhury, 2008; Lin et al., 2014). As the bolus enters the UES, the posterior tongue, epiglottis, and hyolaryngeal complex return to their rest positions

(Perlman & Christensen, 1997; Yoon, Park, Park, & Jung, 2014) with the UES closing after the passing of the bolus tail (Jacob et al., 1989; Lin et al., 2014; Yoon et al., 2014).

The true and false vocal folds abduct, the soft palate lowers and respiration resumes completing the swallowing act (Perlman & Christensen, 1997; Zemlin, 1998).

The vagus nerve. The swallow is executed via six cranial nerves, of which the vagus nerve is central to swallow function (Miller et al., 1997; Zemlin, 1998). Its relevance to the integrity of the swallow is exemplified in those patients experiencing endotracheal intubation and/or CV surgery due to its anatomical location and injury risk during these interventions (Benouaich, Porterie, Bouali, Moscovici, & Lopez, 2012;

Cavo, 1985; Dimarakis & Protopapas, 2004; Gibbin & Egginton, 1981; Hamdan,

Moukarbel, Farhat, & Obeid, 2002; Ishimoto et al., 2002; Itagaki, Kikura, & Sato, 2007;

Murty & Smith, 1989; Myssiorek, 2004; Shafei, el-Kholy, Azmy, Ebrahim, & al-

Ebrahim, 1997; Tewari & Aggarwal, 1996). The vagus nerve has multiple branches of which we will discuss two in detail: the internal branch of the superior laryngeal nerve

(inSLN) and the recurrent laryngeal nerve (RLN). The inSLN passes through the thyroid cartilage with smaller branches innervating the ipsilateral hemilaryngeal mucosa (Rueger,

1972; Stephens, Wendel, & Addington, 1999) including the epiglottis, aryepiglottic folds, glottis (true and false vocals folds), arytenoid mucosa and subglottic mucosa (Rueger,

1972; Stephens et al., 1999). These branches are primarily afferent and integral for the elicitation of various protective reflexes including the laryngeal adductor response (LAR) and laryngeal cough reflex (LCR) (Bradley, 2000; Sulica, 2004; Yoshida, Tanaka,

Hirano, & Nakashima, 2000). In contrast, the RLN has two branches, the right and left,

INTRODUCTION 6

each with differing courses and both with afferent and efferent fibers (Benouaich et al.,

2012). The right branch courses caudally to the right common carotid and subclavian

artery then towards the larynx (Benouaich et al., 2012; Moreau et al., 1998; Zemlin,

1998). The left courses inferiorly making a loop under the lower aortic arch before it moves superiorly between the trachea and esophagus with termination at the larynx

(Benouaich et al., 2012; Moreau et al., 1998; Zemlin, 1998). Together, the two RLN branches innervate all intrinsic laryngeal muscles (except the cricothyroid) and subglottal mucosa (Benouaich et al., 2012; Moreau et al., 1998; Zemlin, 1998) and are key in the movement of glottal structures during swallowing (Cavo, 1985; Gibbin & Egginton,

1981).

Airway protection during the swallow. The upper airway is protected through the movement of laryngeal structures and their reflexive responses, including the LAR

and LCR, as moderated by their respective laryngeal nerve branches (Bradley, 2000;

Sulica, 2004; Yoshida et al., 2000). Laryngeal structural movements, specifically

retroflexion of the epiglottis, the adduction of the true vocal folds (Medda et al., 2003)

and medialization of the aryepiglottic and false vocal folds act as a multi-layered valving

system protecting the airway from prandial aspiration (Benouaich et al., 2012; Cavo,

1985; Gibbin & Egginton, 1981). These laryngeal reflexes are moderated primarily by

the inSLN (Rueger, 1972; Stephens et al., 1999) as initiated through mechanoreceptor

stimulation in the areas of the tongue base, epiglottis, pyriform sinuses and supraglottic

larynx (Bradley, 2000; Rueger, 1972; Stephens et al., 1999; Sulica, 2004; Yoshida et al.,

2000). Both the LAR and LCR help to prevent unwanted material from entering and

therefore compromising the airway. The LAR is a rapid adduction of the vocal folds due

to stimulation of the laryngeal mucosa (Ambalavanar, Tanaka, Selbie, & Ludlow, 2004)

INTRODUCTION 7

thereby quickly closing off access to the upper trachea. The LCR is a cough reflex also

triggered by mechanical stimulation of the larynx or trachea (Bradley, 2000; Rueger,

1972; Stephens et al., 1999; Sulica, 2004; Yoshida et al., 2000). When the LCR is elicited in normal subjects, it results in involuntary coughing and breathing pattern alterations (Nishino, Tagaito, & Isono, 1996; Yoshida et al., 2000). When the LAR or

LCR is absent or require higher than normal thresholds to elicit a response, the risk of aspiration is also higher (Aviv, 1997; Aviv et al., 1997; Cunningham, Halum, Butler, &

Postma, 2007; Setzen et al., 2003; Tabaee et al., 2006). Ultimately, these reflexes can be affected by disease processes or interventions that interrupt their afferent control including gastroesophageal reflux (Mendell & Logemann, 2002; Phua, McGarvey, Ngu,

& Ing, 2005), chronic obstructive pulmonary disease (COPD) (Tsuzuki et al., 2012), stroke (Park, Kim, Ko, & McCullough, 2010), endotracheal intubation and anesthesia

(Hasegawa & Nishino, 1999). Impairment to either the LAR or LCR is a decreased or delayed glottal closure (Mendell & Logemann, 2002; Park et al., 2010), which can lead to airway compromise (Aviv et al., 2002; Tabaee et al., 2006).

Respiration and swallowing. The upper respiratory and deglutitive systems are biomechanically interdependent requiring precise coordination due to their shared anatomy and neurophysiological regulation (Miller, 1982; Sumi, 1963). A typical respiration-swallow cycle is as follows: expiration, swallow initiation, swallow apnea, swallow and then resumption of expiration (Martin-Harris, Brodsky, et al., 2005).

During restful respiration, the true vocal folds abduct facilitating relatively unimpeded air passage throughout the upper and lower airways (Zemlin, 1998). In contrast, during the swallow, a momentary respiratory cessation occurs in concert with the medialization of the true and false vocal folds and epiglottic retroflexion (McFarland & Lund, 1995;

INTRODUCTION 8

Nishino, 2012). The duration of the apneic period ranges from 0.5 - 1.0s (Martin,

Logemann, et al., 1994; Martin-Harris, Brodsky, et al., 2005; Martin-Harris et al., 2003).

At this same time, an alteration in respiratory cycling ensures that expiration occurs after

swallow completion providing added protection for the upper and lower respiratory tracts

from prandial aspiration (McFarland & Lund, 1995; Nishino, 2012).

Respiration will always take biological precedence over deglutition (Selley, Ellis,

Flack, & Brooks, 1990) and in order to minimize airway compromise, respiration will

adapt when in relative proximity to deglutitive acts (Martin-Harris et al., 2003; Preiksaitis

& Mills, 1996; Selley et al., 1990; Selley et al., 1989a). Even as food or fluid approaches the mouth, respiratory cycling is reorganized in order to ensure expiration occurs following the completion of the swallow (Palmer & Hiiemae, 2003; Selley et al., 1989a).

The swallow apneic period occurs consistently after expiration commences in healthy

individuals (Martin, Logemann, et al., 1994; Preiksaitis, Mayrand, Robins, & Diamant,

1992; Preiksaitis & Mills, 1996). It is postulated that this resumption of exhalation

following bolus passage into the esophagus (Martin, Logemann, et al., 1994; Selley et al.,

1989a; Smith, Wolkove, Colacone, & Kreisman, 1989) is a protective mechanism that

facilitates the expulsion of pharyngeal residue following the swallow with an outward

flow of air (Selley et al., 1989a; Smith et al., 1989). Similarly, the cessation of

respiration during the swallow apneic period also serves a protective purpose and it too

may be altered by medical and environmental circumstances (Issa & Porostocky, 1994;

Martin, Logemann, et al., 1994; Martin-Harris, Brodsky, et al., 2005; Martin-Harris et al.,

2003; Preiksaitis et al., 1992; Preiksaitis & Mills, 1996). The duration of the apneic

period is typically bolus size dependent (Issa & Porostocky, 1994; Martin, Logemann, et

al., 1994; Martin-Harris, Brodsky, et al., 2005; Martin-Harris et al., 2003; Preiksaitis et

INTRODUCTION 9

al., 1992; Preiksaitis & Mills, 1996). However, during feeding paradigms that mimic

meals, increasing bolus sizes do not increase the apneic period duration; therefore, some

paradigms have the potential to compromise airway protection in specific patient

populations (Preiksaitis & Mills, 1996). Environmental changes notwithstanding,

respiratory cycling and swallow apneic periodicity can be affected by medical

interventions, particularly secondary to endotracheal intubation and mechanical

ventilation as will be discussed in section II.

Aging. Aging influences the swallow through physiological alterations, sensory changes and attenuation of protective airway reflexes. In general when comparing healthy elderly subjects to a younger cohort, there is an overall prolongation in swallow duration (Robbins, Hamilton, Lof, & Kempster, 1992; Shaw et al., 1995) characterized by increased oral transit time (Shaw et al., 1995; Yoshikawa et al., 2005), pharyngeal transit time and pharyngeal dwell time (Cook et al., 1994; Yoshikawa et al., 2005). Oral stage changes include increased mastication cycles and piecemeal deglutition

(Yoshikawa et al., 2005) resulting in multiple swallows to clear a single bolus, inefficient lingual movements, and inadequate bolus formation (Frederick, Ott, Grishaw, Gelfand, &

Chen, 1996). Pharyngeal differences, when compared to younger cohorts, include delayed initiation of hyolaryngeal elevation (Robbins et al., 1992), increased pharyngeal residue (Cook et al., 1994; Frederick et al., 1996) and increased prevalence of airway

penetration (Frederick et al., 1996; Yokoyama, Mitomi, Tetsuka, Tayama, & Niimi,

2000; Yoshikawa et al., 2005). Swallowing sensory changes associated with aging have

also been explored (Aviv, 1997; Pontoppidan & Beecher, 1960). When conducting

airway sensory testing, Aviv and colleagues (1997) demonstrated higher than normal

thresholds for sensory discrimination and reduced laryngopharyngeal (LP) sensitivity

INTRODUCTION 10

(Aviv, 1997), confirming the progressive loss of protective airway reflexes with age

(Pontoppidan & Beecher, 1960). Other oral and pharyngeal sensory perception affected

by age is the perception of fluid viscosity (Smith, Logemann, Burghardt, Zecker, &

Rademaker, 2006). As a result, regardless of their medical diagnosis, the elderly are a

demographic at increased risk of dysphagia.

Diagnosing Dysphagia

Dysphagia screening. Dysphagia screening is used to identify at-risk patients

(Martino et al., 2005; Martino, Pron, & Diamant, 2000). In the event of screening failure, they are referred for further assessment and a more accurate detailing of the nature and severity of their dysphagia if present (Martino et al., 2005). While many swallowing

screening tools have been validated for use with stroke patients (Martino, Flowers, Shaw,

& Diamant, 2013; Schepp, Tirschwell, Miller, & Longstreth, 2012), at present no

screening tools have been properly psychometrically validated for use in patients following extubation (Macht, Wimbish, Bodine, & Moss, 2013) and as a result, their

ability to predict dysphagia is currently unknown. The three screening methods which

have been used to screen patients for dysphagia following extubation include: 1) the 3-

Ounce Water Swallow Challenge (Leder, Suiter, Warner, & Kaplan, 2011; Suiter &

Leder, 2008) originally used for screening for swallowing impairment following stroke

(DePippo, Holas, & Reding, 1992), 2) the Preliminary Assessment Protocol (Mangilli,

Moraes, & Medeiros, 2012; Padovani, Moraes, Sassi, & de Andrade, 2013) and 3) gag

reflex testing (DeVita & Spierer-Rundback, 1990). Please see Table 1.1. Of these three,

the 3-Ounce Water Swallow Challenge is the only screening tool that has been tested on

extubated patients while using an instrumental criterion reference test (FEES) (Suiter &

Leder, 2008). This study was limited by its retrospective design and restrictive definition

INTRODUCTION 11 of dysphagia while exhibiting a high bias risk with unclear patient enrollment and a lack of assessor blinding.

Table 1.1.

Description and critical appraisal of swallowing screening methods used with patients following extubation.

Screening Criterion Reference Testing

Validity Reliability Likelihood Design and Method Description Etiology Test Blinding Ratio Enrolment Sensitivity Specificity Intrarater Interrater (95% CI)

Patient to The same drink three assessor Retrospective, 3-oz. Water Mixed acute ounces of conducted unclear (referred Swallow 95.5% 49.1% NR NR 1.88 care FEES water from (1.61-2.20) criterion test for swallowing Challenge a patients cup without and screen assessment) interruption concurrently

Thirteen clinical Preliminary conditions b Prolonged Assessment screened for mechanical Prospective, NR NR NR NR NR NR NR Protocol presence ventilation consecutive (PAP) and/or (>48 h) impairment severity

Stimulation of one or both 1.0 (0.9-2.3) Gag reflex Prospective, faucial pillars 47-87% 48-57% NR NR to Stroke VFS NR testing c consecutive in order to 2.1 (1.1-4.7) elicit gag

Note. CI = confidence interval; NR = not reported; FEES = fiberoptic endoscopic evaluation of swallowing; VFS = videofluoroscopic swallowing study. a Study included heterogeneous acute care patients with results reported herein for cardiothoracic patients only (Suiter & Leder, 2008). b PAP clinical conditions include: tube feeding, breathing pattern, breathing and speech coordination, dysphonia, gag reflex, cough reflex, laryngeal elevation, oxygen saturation, supplemental oxygen, speech intelligibility, saliva, dentition and orofacial motor ability (Mangilli et al., 2012). c Psychometric values reported as a range based on a metaanalyses including stroke patients (Martino et al., 2000) as values unknown for recently extubated patients.

A recent nationwide survey was sent to all speech-language pathologists in the US

caring for patients who are or were mechanically ventilated (Macht et al., 2012). The

goal of this survey was to report on SLP practice patterns providing service for this

particular patient population (Macht et al., 2012). Of the respondents, only 41% of

hospitals screen for dysphagia following extubation (Macht et al., 2012). While informal

screening methods are utilized by clinicians who provide medical services for recently

extubated patients (Macht et al., 2012), all dysphagia screening tools have been validated

on patient populations whose etiologies are primarily neurogenic in nature (Martino et

al., 2013; Schepp et al., 2012; Wilkinson, Burns, & Witham, 2012) and as a result, the

predictive value of screening for dysphagia in other populations, including those

following extubation, remains to be determined (Wilkinson et al., 2012).

Clinical swallowing evaluation (CSE). The practice patterns of the speech- language pathologists conducting the CSE throughout the continuum of care were surveyed and results found little use of standardized methods (Martino, Pron, & Diamant,

2004), little consensus on assessment task importance (McCullough, Wertz, Rosenbek, &

Dinneen, 1999) and practice patterns varied widely (Martino et al., 2004). With only one

standardized assessment tool available for clinical swallowing evaluations (Mann

Assessment of Swallowing Ability [MASA]; Mann, 2002), which was validated with stroke patients, clinicians need to rely on an informal approach.

Components of the CSE vary across clinicians and their reliability has been

questioned (McCullough et al., 2000). Regardless, some CSE components have shown

diagnostic value across different patient groups. They include: 1) detailed clinical,

medical and medication history (Castell & Donner, 1987; McCullough & Martino, 2013),

2) oral motor evaluation (Mann & Hankey, 2001; McCullough & Martino, 2013; Murray,

INTRODUCTION 14

1999), 3) laryngeal function assessment including volitional cough (Daniels, Ballo,

Mahoney, & Foundas, 2000; Horner, Brazer, & Massey, 1993; Schroeder, Daniels,

McClain, Corey, & Foundas, 2006) and voice assessment (Linden, Kuhlemeier, &

Patterson, 1993; McCullough, Wertz, & Rosenbek, 2001), 4) assessment of secretion management (Langmore et al., 1998; Murray, Langmore, Ginsberg, & Dostie, 1996) and lastly, 5) the inclusion of trial swallows if deemed clinically appropriate (McCullough &

Martino, 2013). In reference to recently extubated patients in particular, clinicians focus their CSE to include: case history along with patient interview, dentition, secretion management, oral motor function, and clinical assessment of oral (efficiency, lip seal) and pharyngeal (delay, vocal quality) function using food and fluid trials consisting of multiple textures (Macht et al., 2012).

Following a nationwide survey on practice patterns of SLPs providing service for mechanically ventilated patients, only 3% of the respondents report that they receive CSE referrals for all recently extubated patients with 29% reporting that dysphagia referral

guidelines exist for these patients in their respective hospitals (Macht et al., 2012).

Following extubation, SLPs reported waiting a median time of 24 hours prior to

conducting a CSE with 60% of the respondents reporting that a CSE was the primary

diagnostic method for determining post-extubation dysphagia (Macht et al., 2012).

Similar to dysphagia screening, the only standardized CSE have been validated on the

stroke population (Mann, 2002) with a standardized protocol yet to be psychometrically

validated for use with patients following exutbation. In Brazil, the Dysphagia Risk

Evaluation Protocol (DREP) (Padovani, Moraes, Mangili, & de Andrade, 2007) in

conjunction with the Prelimary Assessment Protocol and oral feeding trials are being

utilized as a full clinical swallowing assessment for recently extubated patients (Padovani

INTRODUCTION 15

et al., 2013) however, their psychometric properties are yet to be determined. Hence,

adjunct examination of the swallow by way of objective instrumentation is warranted

particularly for patients at high risk of pharyngeal impairments with or without silent

aspiration (McCullough, Wertz, & Rosenbek, 2001; Noordally, Sohawon, De Gieter,

Bellout, & Verougstraete, 2011) such as those who have experienced prolonged

intubation.

Instrumental swallowing assessments. Instrumental methods of assessing

swallow function include the videofluoroscopic swallow study (VFS) (Logemann, 1993,

1997) and fiberoptic endoscopic evaluation of the swallow (FEES) (Langmore, Schatz, &

Olsen, 1988; Langmore, Schatz, & Olson, 1991). Not only is instrumentation used to

discern the integrity of the swallow and to ascertain potential cause of airway

compromise, it also affords clinicians the opportunity to assess any possible benefit from

interventions such as those involving bolus texture, volume, and administration

modifications and/or compensatory strategies (Martin-Harris, Logemann, McMahon,

Schleicher, & Sandidge, 2000).

The instrumentation most widely available to SLPs providing service to mechanically ventilated patients is videofluoroscopy (98%) followed by endoscopy

(41%) (Macht et al., 2012). Where available, the VFS is used to assess dysphagia in approximately 40% of referred patients following extubation (Macht et al., 2012) as compared to a slightly lower utilization with neurological patients at 36% (Martino et al.,

2004). Hospitalized patients requiring mechanical ventilation, with or without tracheotomy, have an increased risk of silent aspiration thereby necessitating more careful inspection of airway compromise with instrumental assessment (Davis &

Thompson Stanton, 2004; Elpern, Scott, Petro, & Ries, 1994; Tolep et al., 1996). While

INTRODUCTION 16

both VFS and FEES provide a comprehensive assessment of swallow function and

determine the efficacy of therapeutic strategies, each offer a unique diagnostic

perspective (Aviv, 2000b; Hiss & Postma, 2003; Kidder, Langmore, & Martin, 1994;

Langmore, 2003; Logemann, 1993; Logemann, Rademaker, Pauloski, Ohmae, &

Kahrilas, 1998). The following sections describe each method along with their relative advantages and weaknesses.

The videofluoroscopic swallow study. The widely accepted gold standard for

instrumental swallowing evaluations of the oral, pharyngeal and upper esophageal phases

of the swallow is the VFS (Martin-Harris et al., 2000; McCullough et al., 2005). Using

videofluoroscopy, Dr. Jeri Logemann adapted the original radiographic swallowing

assessment, barium cineradiography (Donner & Siegel, 1965; Ramsey, Watson, Gramiak,

& Weinberg, 1955), with her procedure and protocol still used routinely (Logemann,

1993, 1997). The VFS affords a dynamic and continuous view of the structures involved

in the swallow (Dodds et al., 1990; Logemann, 1993, 1997). The procedure typically

involves a speech-language pathologist, radiologist and x-ray technician while taking

place in a diagnostic imaging suite outfitted with a fluoroscopy unit (Logemann, 1993).

A regulated amount of food and fluid mixed with barium contrast is given to the patient

while the fluoroscopy unit captures its movement from the oral cavity to beyond the

upper esophageal sphincter (Logemann, 1993). Two views can be obtained during the

VFS, lateral and anterior-posterior, and whether one or both views are conducted is

dependent upon the mobility of the patient, the accommodation of the equipment and the

assessment goals of the VFS (Logemann, 1993, 1997). With the current digital

fluoroscopic technologies, capture rates using a pulse of 30 frames per second with high

resolution recording are recommended (Bonilha et al., 2013).

INTRODUCTION 17

Serial radiographic images of the oral cavity, pharynx, upper airway and proximal

esophagus are captured in sequence while the patient swallows barium-contrasted food and/or liquid (Dodds et al., 1990; Logemann, 1993, 1997). The clinician conducting the study may espouse either a regimented (Lazarus et al., 1993; Logemann, 1993) or more patient-led approach (Linden & Siebens, 1983) with bolus textures, volume and order of presentation are at their discretion. Regardless, protocol components vary across institutions particularly regarding the textures (Martino et al., 2004) and the barium concentrations used (Stokely, Molfenter, & Steele, 2014). In addition, the reliability of videofluoroscopic swallowing interpretation has long been described as poor

(McCullough, Wertz, Rosenbek, et al., 2001; Stoeckli, Huisman, Seifert, & Martin-

Harris, 2003) including poor interrater reliability for airway compromise ratings with intraclass correlation coefficients ranging from 0.01 to 0.65 (McCullough et al., 2001) .

However, efforts are being made to standardize the procedural protocol (Lazarus et al.,

1993; Logemann, 1993, 1997; Martin-Harris et al., 2008; Martin-Harris et al., 2000) and its interpretation (Leonard, Kendall, McKenzie, Goncalves, & Walker, 2000; Martin-

Harris et al., 2008; Rosenbek, Robbins, Roecker, Coyle, & Wood, 1996).

Two recent approaches have targeted interpretation objectivity and rater reliability, namely: 1) through the use of rating scales or scoring systems (Eisenhuber et al., 2002; Martin-Harris et al., 2008; Molfenter & Steele, 2013; Pearson, Molfenter,

Smith, & Steele, 2013; Rosenbek et al., 1996) or 2) through the digital measurement of structural movements during the swallow (Allen, White, Leonard, & Belafsky, 2010;

Leonard, Rees, Belafsky, & Allen, 2009; Leonard et al., 2000; Steele et al., 2011).

Individually, each method assesses different aspects of the swallow. The VFS rating scales or scoring systems each evaluate a different aspect of the swallow using

INTRODUCTION 18

videofluoroscopic (VF) images (Eisenhuber et al., 2002; Martin-Harris et al., 2008;

Molfenter & Steele, 2013; Pearson et al., 2013; Rosenbek et al., 1996) ranging from rating structural movement involved in all stages of the swallow (Martin-Harris et al.,

2008), to more specific aspects such as airway protection (Rosenbek et al., 1996) or the quantification of oropharyngeal residue (Eisenhuber et al., 2002; Molfenter & Steele,

2013; Pearson et al., 2013). Of these methods, two are psychometrically validated: the

Modified Barium Swallow Measurement Tool for Swallow Impairment (MBSImpTM©,

Northern Speech Services, Gaylord, MI) (Martin-Harris et al., 2008) and the Penetration-

Aspiration Scale (PAS)(Rosenbek et al., 1996). The MBSImpTM© is comprised of 17

different components that together describe oral, pharyngeal and esophageal function.

The PAS is an 8-point interval scale that describes the degree to which material has

invaded the airway and whether the material has been ejected. Together, the

MBSImpTM© and PAS quantify swallowing impairment severity and airway protection respectively.

The MBSImpTM© is the first and only swallowing impairment rating tool of its

kind which has been psychometrically validated (Martin-Harris et al., 2008). Its aim is to

assist the clinician with the interpretation of the underlying swallowing physiology

thereby assisting with intervention approaches (Martin-Harris et al., 2008). The tool’s

authors confirm construct and external validity through their confirmatory factor analysis and validation against external surrogate measures of swallowing and nutrition along with high (>80%) intra- and interrater concordance for blinded ratings of the VFS

(Martin-Harris et al., 2008). During the validation study for the MBSImpTM©, the chosen

patient eligibility criteria and the VFS protocol closely aligned with the patients and

protocols seen in clinical practice (Martin-Harris et al., 2008). While the MBSImpTM©

INTRODUCTION 19 provides information regarding the physiology underlying the potential airway compromise, it does not elaborate on the degree of airway invasion or the patient’s response (Martin-Harris et al., 2008). As a result, the authors of the MBSImpTM© suggest using the PAS (Rosenbek et al., 1996) in concert with the MBSImpTM© (Martin-Harris et al., 2008).

The PAS is used to quantify airway invasion using VF images (Rosenbek et al.,

1996). In their seminal study, the authors reported average interjudge intraclass Kappa coefficients ranging from 0.35 to 0.88 with intrajudge coefficients ranging from 0.21 to

1.0 (Rosenbek et al., 1996). Following its development using stroke, head and neck cancer patients as well as healthy subjects, it was validated using four judges on multiple swallows recorded from healthy older subjects along with stroke patients (Rosenbek et al., 1996). The scale has been utilized widely in both research and clinical practice and with numerous patient populations (Allen et al., 2010; Bhattacharyya, Kotz, & Shapiro,

2003; Colodny, 2002; Cvejic et al., 2011; Hutcheson et al., 2012; Martin-Harris et al.,

2008; Molfenter & Steele, 2013; Troche, Brandimore, Okun, Davenport, & Hegland,

2014).

While the MBSImpTM© and PAS provide a rating for aspects of the patient’s swallow, they do not objectively measure structural movement during the swallow.

Individual VF images can be extracted from the VFS and used to conduct image-based measurements of various structures involved in swallowing (Perlman, VanDaele, &

Otterbacher, 1995) including hyoid bone displacement (Leonard, 2007; Leonard et al.,

2000; Molfenter & Steele, 2014; Perlman et al., 1995; Steele et al., 2011) and pharyngeal wall constriction (Leonard, 2007; Leonard et al., 2000). Adequate hyoid elevation (Jacob et al., 1989; Kim & McCullough, 2008; Leonard, 2007; Steele et al., 2011) and

INTRODUCTION 20 pharyngeal constriction (Leonard, Kendall, & McKenzie, 2004; Leonard, 2007; Leonard et al., 2009; Leonard et al., 2000; Setzen et al., 2003; Yip, Leonard, & Belafsky, 2006) are associated with successful propulsion of food or fluid through the pharynx into the esophagus thereby preventing laryngeal penetration, tracheal aspiration and/or pharyngeal residue. There are numerous methods to measure hyoid excursion (Molfenter

& Steele, 2012; Molfenter & Steele, 2014) and one published method to measure pharyngeal constriction (Leonard et al., 2004; Leonard, 2007; Leonard et al., 2009;

Leonard et al., 2000). Two of the most recently published methods for measuring anterior and superior hyoid excursion include reporting: 1) the displacement as a trajectory in absolute units (Leonard, 2007; Leonard et al., 2000) or alternatively 2) the movement with an anatomical scalar as a reference (Molfenter & Steele, 2014; Steele et al., 2011). Pharyngeal constriction is measured by way of a ratio that compares the area of the pharynx at rest with that of it at its most constricted during the swallow (Leonard et al., 2004; Leonard, 2007; Leonard et al., 2009; Leonard et al., 2000). These displacement measures may in turn assist in determining possible treatment approaches in order to remediate specific swallow deficiencies.

Fiberoptic endoscopic evaluation of the swallow. Fiberoptic endoscopic evaluation of the swallow (FEES) was first published as a dysphagia assessment method in 1988 (Langmore et al., 1988). Presently it is receiving increasing acceptance as a viable alternative to the VFS (Hiss & Postma, 2003; Langmore, 2003; Macht et al.,

2012). It typically involves a speech-language pathologist along with an otolaryngologist or physician trained in the procedure (Langmore, 2003; Langmore et al., 1988). The SLP and physician have complementary responsibilities during the procedure with the

INTRODUCTION 21 physician rendering pertinent medical diagnoses and the SLP diagnosing and managing the dysphagia (ASHA, 2000).

FEES utilizes flexible nasendoscopy where the scope is passed through the nasopharynx and is suspended above the epiglottis (Langmore et al., 1988). It provides a direct view of the hypopharynx and larynx along with the superior aspects of the upper trachea and upper esophageal sphincter (Langmore et al., 1988; Langmore et al., 1991;

Murray et al., 1996). Similar to the VFS protocol, the patient is given a variety of bolus sizes and textures including both solid and liquid depending upon patient tolerance

(Langmore et al., 1988). Different from VFS, the feeding trials are not mixed with a radiopaque medium, rather food colouring in order to differentiate the bolus from the surrounding mucosa (Langmore et al., 1988; Langmore et al., 1991). While the use of coloured dye in enteral tube feeding has had detrimental health effects (Maloney & Ryan,

2002; Maloney et al., 2002), the limited quantity utilized throughout the FEES procedure has not resulted in any documented medical complications.

Several protocols and scoring systems have been developed for FEES (Langmore,

2011; Murray, 1999). Parameters assessed include the adequacy of structural movement in relation to bolus position, secretions, airway protection and mucosal integrity

(Langmore, 2011; Murray, 1999). Currently, there are no psychometrically validated tools for the interpretation of FEES.

Fiberoptic endoscopic evaluation of the swallow with sensory testing. The

FEES procedure may also be expanded to include a sensory testing component (Aviv,

2000a; Aviv et al., 2000; Aviv, Kim, Sacco, et al., 1998; Aviv, Kim, Thomson, et al.,

1998; Aviv et al., 2002). Laryngopharyngeal sensory thresholds are assessed using measured air pulses as delivered through a nasendoscopy scope equipped with a separate

INTRODUCTION 22 air channel (Aviv, 2000a; Aviv et al., 2000; Aviv, Kim, Sacco, et al., 1998; Aviv, Kim,

Thomson, et al., 1998; Aviv et al., 2002). These are delivered to the aryepiglottic folds in an attempt to elicit the laryngeal adductor reflex (LAR) (Aviv, 2000a; Aviv et al., 2000;

Aviv, Kim, Sacco, et al., 1998; Aviv, Kim, Thomson, et al., 1998; Aviv et al., 2002). The greater air pressure required to elicit the LAR, the greater the laryngeal sensory loss

(Aviv, 1997; Aviv, Kim, Sacco, et al., 1998; Aviv et al., 1997; Aviv et al., 2002). The normal sensory threshold in order to elicit the LAR is <4.0 mmHg (Aviv et al., 2000;

Aviv, Kim, Thomson, et al., 1998; Aviv et al., 2002). Apart from sensory threshold testing on neurogenic and mixed patient populations (Aviv et al., 2000; Aviv et al.,

1997), no study has determined sensory thresholds in patients following extubation and its relationship to their airway protection and swallowing physiology.

VFS versus FEES: which to choose? The instrumental tool of choice is often based on the diagnostic needs of the clinician, the medical status of the patient or equipment accessibility (Hiss & Postma, 2003; Langmore, 2003; Langmore et al., 1988;

Langmore et al., 1991). While patients can be managed equally well with either VFS or

FEES (Aviv, 2000b), when compared to VFS, FEES contributes different information regarding swallow physiology which may provide diagnostic and therapeutic value for certain populations (Hiss & Postma, 2003; Kelly, Drinnan, & Leslie, 2007; Kelly, Leslie,

Beale, Payten, & Drinnan, 2006; Langmore, 2003; Langmore et al., 1988; Murray et al.,

1996; Wu, Hsiao, Chen, Chang, & Lee, 1997). This is particularly true for patients who have undergone medical interventions, such as endotracheal intubation, that may affect their upper airway structural integrity and physiology. In addition, FEES may be more appropriate for particular clinical situations for example when assessing patients with restricted mobility or for those unable to leave their care unit due to medical fragility,

INTRODUCTION 23 recent extubation or critical illness (Ajemian, Nirmul, Anderson, Zirlen, & Kwasnik,

2001; Leder, Cohn, & Moller, 1998; Noordally et al., 2011). When compared to VFS,

FEES is arguably a more sensitive tool for identifying airway penetration, aspiration, and/or residue (Kelly et al., 2007; Kelly et al., 2006; Wu et al., 1997) along with assessing retained pharyngeal secretions (Murray et al., 1996) or mucosal abnormalities

(Langmore et al., 1988; Langmore et al., 1991). When comparing the influence of instrumental assessment method on the interpretation of penetration, aspiration and residue using raters blinded to each other and clinical information, scores were significantly higher for FEES examinations when compared to VFS (Kelly et al., 2007;

Kelly et al., 2006). Since FEES does not involve radiation exposure, it can be conducted for as long as the patient will tolerate scope placement (Hiss & Postma, 2003; Langmore,

2003; Leder, 1998). As a result, this procedure may evaluate fatigue or practice effects over the course of a meal or completed serially in order to evaluate swallow recovery

(Hiss & Postma, 2003; Langmore, 2011; Langmore, 2003; Langmore et al., 1988;

Langmore et al., 1991; Murray, 1999). When comparing costs, FEES is more economic when compared to VFS due to comparatively lower equipment and personnel costs (Aviv et al., 2001). However, VFS is recommended if the goals either individually or in combination are to 1) assess oral and pharyngeal physiology in concert (Logemann et al.,

1998), 2) use standardized methods of interpretation (Martin-Harris et al., 2008;

Rosenbek et al., 1996), or 3) conduct structural displacement measurements (Leonard,

2007; Leonard et al., 2000).

INTRODUCTION 24

II. Endotracheal Intubation and Mechanical Ventilation

Background

In 2000, approximately 250,000 patients in the US required prolonged mechanical

ventilation (PMV) for durations exceeding 96 hours during acute illness (Zilberberg, de

Wit, Pirone, & Shorr, 2008). In Ontario by the year 2026, it is projected that the number

requiring PMV will increase by 80% when compared to the incidence in 2006 (Needham

et al., 2005). PMV is a medical necessity and in 2003, its usage in the US accrued costs

of over $16 billion annually, accounting for nearly two-thirds of all healthcare costs

(Zilberberg & Shorr, 2008). Following discharge from acute care, those requiring PMV

continue to have functional disability necessitating ongoing medical care (Chelluri et al.,

2004; Garland et al., 2004; Herridge et al., 2011; Myhren, Ekeberg, & Stokland, 2010).

As a result, early diagnosis of the comorbidities that occur following PMV, such as

dysphagia (Ajemian et al., 2001; Barker, Martino, Reichardt, Hickey, & Ralph-Edwards,

2009; Leder, Cohn, et al., 1998; Tolep et al., 1996), will minimize complications and improve patient outcomes (Needham et al., 2005).

Dysphagia Following Endotracheal Intubation

It is widely accepted that dysphagia is prevalent in a variety of medical conditions including stroke (Martino et al., 2005), head and neck cancer (Ward, Bishop, Frisby, &

Stevens, 2002), closed head injuries (Lazarus & Logemann, 1987), spinal cord injuries

(Abel, Ruf, & Spahn, 2004; Kirshblum, Johnston, Brown, O'Connor, & Jarosz, 1999;

Wolf & Meiners, 2003) or cervical spine surgery (Lee, Bazaz, Furey, & Yoo, 2007;

Smith-Hammond et al., 2004; Tervonen et al., 2007). While dysphagia has been reported to occur in as many as 84% of patients following mechanical ventilation (Macht et al., 2011), when compared to other patient populations, relatively little has been

INTRODUCTION 25

published in this area (Ajemian et al., 2001; Atkins et al., 2010; Atkins et al., 2007;

Barker et al., 2009; Barquist, Brown, Cohn, Lundy, & Jackowski, 2001; Bordon et al.,

2011; Brodsky et al., 2014; Brown et al., 2011; de Larminat, Montravers, Dureuil, &

Desmonts, 1995; de Medeiros, Sassi, Mangilli, Zilberstein, & de Andrade, 2014; DeVita

& Spierer-Rundback, 1990; El Solh, Okada, Bhat, & Pietrantoni, 2003; Elpern et al.,

1994; Ferraris et al., 2001; Hafner, Neuhuber, Hirtenfelder, Schmedler, & Eckel, 2008;

Harrington et al., 1998; Keeling et al., 2007; Kwok et al., 2013; Leder, Cohn, et al., 1998;

Macht, King, et al., 2013; Macht et al., 2011; Messina et al., 1991; Murty & Smith, 1989;

Padovani, Moraes, de Medeiros, de Almeida, & de Andrade, 2008; Rousou et al., 2000;

Tolep et al., 1996). Though the adverse effect of artificial airways on swallowing

function is debatable (Barquist et al., 2001; Leder & Ross, 2000), swallowing

impairments have been documented following prolonged oral endotracheal intubation

(Ajemian et al., 2001; Barker et al., 2009; El Solh et al., 2003; Hogue et al., 1995;

Rousou et al., 2000), tracheotomy (Bonanno, 1971; DeVita & Spierer-Rundback, 1990)

and mechanical ventilation (DeVita & Spierer-Rundback, 1990; Elpern et al., 1994;

Macht et al., 2011; Tolep et al., 1996).

Dysphagia frequency following endotracheal intubation varies widely in the literature from 3% (Ferraris et al., 2001) to greater than 80% (Macht et al., 2011; Tolep et al., 1996). Post-extubation dysphagia has been documented across various diagnostic groups including critical illness (Ajemian et al., 2001; Barquist et al., 2001; Brodsky et al., 2014; de Larminat et al., 1995; de Medeiros et al., 2014; DeVita & Spierer-Rundback,

1990; El Solh et al., 2003; Hafner et al., 2008; Macht et al., 2011; Padovani et al., 2008;

Partik et al., 2000; Tolep et al., 1996), trauma (Bordon et al., 2011; Brown et al., 2011;

Kwok et al., 2013; Leder, Cohn, et al., 1998), organ transplantation (Atkins et al., 2010;

INTRODUCTION 26

Atkins et al., 2007; Helenius-Hietala et al., 2013; Murty & Smith, 1989; Skoretz,

Graham, Kamitomo, & Martino, 2010), thoracic surgery (Davis & Cullen, 1974; Keeling et al., 2007), orthopedics (Stanley, Bastianpillai, Mulcahy, & Langton, 1995), neurogenic diseases (Macht, King, et al., 2013; Padovani et al., 2007), and cardiovascular surgery

(Barker et al., 2009; Burgess, Cooper, Marino, Peuler, & Warriner, 1979; Ferraris et al.,

2001; Harrington et al., 1998; Hogue et al., 1995; Messina et al., 1991; Partik et al., 2003;

Rousou et al., 2000; Skoretz & Rebeyka, 2009; Skoretz, Yee, & Martino, 2012). Few studies are prospective (Barquist et al., 2001; Brodsky et al., 2014; Brown et al., 2011;

Burgess et al., 1979; Davis & Cullen, 1974; El Solh et al., 2003; Hogue et al., 1995;

Kwok et al., 2013; Stanley et al., 1995) with some basing dysphagia frequency on a heterogeneous patient subset referred for swallowing assessments (de Medeiros et al.,

2014; Hafner et al., 2008; Macht, King, et al., 2013; Macht et al., 2011; Moraes, Sassi,

Mangilli, Zilberstein, & de Andrade, 2013). Intubation times have been reported in few studies (Ajemian et al., 2001; Barker et al., 2009; Barquist et al., 2001; El Solh et al.,

2003; Hogue et al., 1995; Leder, Cohn, et al., 1998; Rousou et al., 2000) and a variety of diagnostic methods are utilized across studies with many conducting assessments at undeclared time intervals following extubation (Barker et al., 2009; Brodsky et al., 2014;

Ferraris et al., 2001; Hogue et al., 1995; Macht, King, et al., 2013; Macht et al., 2011;

Rousou et al., 2000). We will discuss each of these limitations in turn.

Studies reporting on post-extubation dysphagia are limited by their patient sample and their failure to declare intubation durations across the population. The studies often include heterogeneous patient populations (Ajemian et al., 2001; Barquist et al., 2001;

Bordon et al., 2011; Brown et al., 2011; Davis & Cullen, 1974; de Larminat et al., 1995;

Keeling et al., 2007; Kwok et al., 2013; Leder, Cohn, et al., 1998; Padovani et al., 2008)

INTRODUCTION 27 with diagnoses commonly known to cause dysphagia (Abel et al., 2004; Kirshblum et al.,

1999; Lazarus & Logemann, 1987; Martino et al., 2005; Ward et al., 2002; Wolf &

Meiners, 2003). For example, many studies have included patients with neurogenic diagnoses (Bordon et al., 2011; Brown et al., 2011; Hafner et al., 2008; Kwok et al.,

2013; Macht, King, et al., 2013; Tolep et al., 1996), head and/or neck malignancies

(Keeling et al., 2007) and in-situ tracheostomies (Bordon et al., 2011; Brown et al., 2011;

DeVita & Spierer-Rundback, 1990; Hafner et al., 2008; Harrington et al., 1998; Hogue et al., 1995; Macht, King, et al., 2013; Tolep et al., 1996). In addition, few studies declare intubation durations across their patient sample (Ajemian et al., 2001; Barker et al., 2009;

Barquist et al., 2001; El Solh et al., 2003; Hogue et al., 1995; Leder, Cohn, et al., 1998;

Rousou et al., 2000). As a result, dysphagia frequency estimates following extubation according to diagnosis are likely imprecise and the relation between intubation duration and dysphagia remains unclear.

Methods utilized by SLPs in order to assess swallowing impairments vary (Macht et al., 2012; Martino et al., 2004), particularly when assessing swallowing following mechanical ventilation (Macht et al., 2012). At present, screening and clinical swallowing evaluation tools have yet to be psychometrically validated on patients following extubation and as a result, standardized practice is lacking (Macht et al., 2012).

In the published literature, the diagnostic methods used to assess patients’ swallowing following extubation ranges from swallowing screening, clinical swallowing assessments

(Bordon et al., 2011; Brodsky et al., 2014; Brown et al., 2011; de Medeiros et al., 2014;

Kwok et al., 2013; Macht, King, et al., 2013; Macht et al., 2011; Moraes et al., 2013) to instrumental assessments including chest radiographs (Burgess et al., 1979; Davis &

Cullen, 1974; Stanley et al., 1995), barium cineradiography (Hogue et al., 1995; Rousou

INTRODUCTION 28

et al., 2000), FEES (Ajemian et al., 2001; Barquist et al., 2001; El Solh et al., 2003;

Hafner et al., 2008; Leder, Cohn, et al., 1998), VFS (Barker et al., 2009; Ferraris et al.,

2001; Keeling et al., 2007) and swallowing latency measurements (de Larminat et al.,

1995). In some studies, multiple assessment methods are utilized (Barker et al., 2009;

Barquist et al., 2001; Ferraris et al., 2001; Harrington et al., 1998; Hogue et al., 1995;

Tolep et al., 1996) with many of the utilized methods, such as static radiographs (Burgess et al., 1979; Davis & Cullen, 1974) and latency measurements (de Larminat et al., 1995), lacking in sensitivity and specificity. The timing of dysphagia assessment across studies varies from immediately following extubation (Burgess et al., 1979; de Larminat et al.,

1995) to assessment upon discharge (Brodsky et al., 2014). Some studies do not declare assessment timing in relation to extubation timing (Barker et al., 2009; Ferraris et al.,

2001; Hogue et al., 1995; Rousou et al., 2000). Due to rapid change in the patient’s status following extubation (de Larminat et al., 1995), consistent assessment timing is crucial. Without consistent assessment methods with adequate precision (Whiting,

Rutjes, Reitsma, Bossuyt, & Kleijnen, 2003; Whiting et al., 2006) or timing of post- extubation evaluations, the accuracy of reported dysphagia frequency is questionable.

Dysphagia characteristics. Swallowing physiology following mechanical ventilation is described in the literature using various methods. From impairment based on clinical observation (de Medeiros et al., 2014; Macht, King, et al., 2013; Macht et al.,

2011; Moraes et al., 2013; Padovani et al., 2007) to limited dysphagia descriptions following the use of instrumentation (Hafner et al., 2008; Leder, Cohn, et al., 1998), no study to date has described both oral and pharyngeal post-extubation swallowing physiology using psychometrically validated measures. Following clinical assessment, dysphagia severity following extubation has been rated as moderately-severe in the

INTRODUCTION 29 majority of patients (Macht, King, et al., 2013; Macht et al., 2011) with primary clinical signs including post-swallow coughing (de Medeiros et al., 2014; Kwok et al., 2013;

Padovani et al., 2007) and voice change (de Medeiros et al., 2014; Kwok et al., 2013).

Reporting dysphagia characteristics based solely on clinical assessment can be questionable (McCullough et al., 2000). For example, one study reports the frequency of silent aspiration and pharyngeal residue without the use of instrumentation (Kwok et al.,

2013), both of which are impossible to confirm based on clinical observation alone.

Following instrumental assessments, many studies define dysphagia primarily as penetration or aspiration (Burgess et al., 1979; Davis & Cullen, 1974; Ferraris et al.,

2001; Hafner et al., 2008; Stanley et al., 1995) with aspiration frequencies ranging from

45% (Leder, Cohn, et al., 1998) to 90% (Hogue et al., 1995). Even with instrumentation, most dysphagia is characterized using general descriptions that are not operationally defined (de Larminat et al., 1995; Ferraris et al., 2001; Leder, Cohn, et al., 1998; Rousou et al., 2000). For example, the swallowing impairment is characterized with nonspecific terms such as delay (de Larminat et al., 1995) or oral and/or pharyngeal abnormalities

(Ferraris et al, 2001). As a result, it is difficult to understand post-extubation swallowing physiology, the mechanisms underlying dysphagia and possible methods of remediation.

Consequences of dysphagia. The medical status of patients following extubation is often tenuous (Blackwood et al., 2011) and when present, dysphagia and its sequelae can lead to higher rates of mortality (Cabré et al., 2010; DeVita & Spierer-Rundback,

1990; Macht, King, et al., 2013; Macht et al., 2011), increased hospitalization costs

(Altman et al., 2010; Cichero & Altman, 2012; Ferraris et al., 2001; Semenov, Starmer,

& Gourin, 2012; Starmer et al., 2014) and poor patient outcomes (Barker et al., 2009;

Brown et al., 2011; Macht, King, et al., 2013; Macht et al., 2011; Rashkin & Davis,

INTRODUCTION 30

1986). In-hospital mortality for those with severe post-extubation dysphagia is

significantly higher when compared to those without the disorder (Macht et al., 2011).

Regardless of the underlying diagnosis, mortality at 1 year following hospital discharge is

28% higher in those with dysphagia as opposed to those without (Cabré et al., 2010).

Post-extubation dysphagia impacts a patient’s nutritional status by delaying resumption of oral intake (Barker et al., 2009; Ferraris et al., 2001; Hafner et al., 2008; Macht, King,

et al., 2013; Macht et al., 2011) and hospital discharge (Barker et al., 2009; Brown et al.,

2011; Macht, King, et al., 2013; Macht et al., 2011). These prolonged hospitalizations

due to dysphagia incur greater costs (Altman et al., 2010; Cichero & Altman, 2012;

Ferraris et al., 2001; Semenov et al., 2012; Starmer et al., 2014). In the US, it is

estimated the increased length of stay secondary to dysphagia alone incurs $547 million

of additional care charges annually (Altman et al., 2010). Poor patient outcomes associated with post-extubation dysphagia include increased rates of pneumonia (Brown et al., 2011; Kwok et al., 2013; Macht, King, et al., 2013), reintubation (Barker et al.,

2009; Kwok et al., 2013; Macht, King, et al., 2013; Macht et al., 2011), and aspiration

(Ajemian et al., 2001; Harrington et al., 1998; Hogue et al., 1995; Leder, Cohn, et al.,

1998). Whether the etiology of aspiration is prandial in nature (Lundy et al., 1999;

Smith, Logemann, Colangelo, Rademaker, & Pauloski, 1999) or of contaminated oral

secretions (Marik, 2001, 2006; Marik, 2011; Marik & Kaplan, 2003; Murray et al., 1996),

it can increase a patient’s risk of developing pneumonia (Loeb, McGeer, McArthur,

Walter, & Simor, 1999; Lundy et al., 1999; Martino et al., 2005; Starmer et al., 2014).

Dysphagia, particularly in the presence of other medical comorbidities, is a

significant predictor for aspiration pneumonia (Cabré et al., 2014; Hibberd, Fraser,

Chapman, McQueen, & Wilson, 2013; Langmore et al., 1998; Marik & Kaplan, 2003;

INTRODUCTION 31

Martin, Corlew, et al., 1994). According to the US National Hospital Discharge Survey,

the relative risk of aspiration pneumonia in patients with dysphagia is approximately nine

times greater when compared to those who do not have the disorder (Altman et al., 2010).

Following stroke, the risk of developing pneumonia is eleven times greater in patients

who aspirate compared to similar patients who do not (Martino et al., 2005). Aspiration

pneumonia also increases readmissions to the intensive care unit (Kozlow, Berenholtz,

Garrett, Dorman, & Pronovost, 2003) and hospital (Cabré et al., 2014) and is associated

with increased hospitalization durations and care costs (Kozlow et al., 2003). Following

surgery, aspiration pneumonia increases the average hospital length of stay by five times

(25 days versus 5 days) and hospitalization costs by four times ($58,000 USD versus

$14,000) (Kozlow et al., 2003). In Canada, the mean healthcare costs of aspiration

pneumonia per patient can run as high as $94,000 (Sutherland, Hamm, & Hatcher, 2010).

Aspiration and its adverse outcomes impacts the recovery of the critically ill (Cameron,

Mitchell, & Zuidema, 1973; Christ et al., 2006; Shifrin & Choplin, 1996) particularly

those who have undergone mechanical ventilation (Almirall, Cabré, & Clavé, 2012;

DeVita & Spierer-Rundback, 1990; Elpern et al., 1994; Kozlow et al., 2003; Spray,

Zuidema, & Cameron, 1976; Tolep et al., 1996). Therefore early multi-disciplinary involvement with this patient group is essential (Marsh, Bertanou, Suominen, &

Venkatachalam, 2010; Starks & Harbert, 2011).

In an attempt to mitigate the ill-effects of aspiration pneumonia, specifically the increased cost of care, hospital protocols now include speech-language pathology led assessments and interventions (Marsh et al., 2010; Starks & Harbert, 2011). There is emerging evidence that the frequency of pneumonia following CV surgery has been reduced with SLP-lead protocol targeting oral care and mandatory swallowing

INTRODUCTION 32

assessments following extubation (Starks & Harbert, 2011). In Great Britain alone these

SLP led initiatives have reduced annual hospitalization costs incurred by iatrogenic

respiratory infections from 48.2 million GBP to 26.1 million (Marsh et al., 2010).

Etiology of Post-extubation Dysphagia

Endotracheal intubation. Endotracheal intubation, particularly of prolonged

durations, is an independent predictor of dysphagia (Barker et al., 2009; Bordon et al.,

2011; Brodsky et al., 2014; Hogue et al., 1995; Kwok et al., 2013; Macht, King, et al.,

2013). In trauma patients, the odds of dysphagia following extubation increased nearly

three-fold with every additional day of mechanical ventilation (Kwok et al., 2013).

While some studies dispute the relation between dysphagia and mechanical ventilation

duration (Barquist et al., 2001) or the use of artificial airways (Leder & Ross, 2000),

there is general consensus, albeit based on only a few studies, that increasing intubation

durations increase the frequency of dysphagia (Barker et al., 2009; Bordon et al., 2011;

Brodsky et al., 2014; Hogue et al., 1995; Kwok et al., 2013; Macht, King, et al., 2013).

Despite this, there is little consensus, either in the mechanical ventilation or dysphagia

literature regarding the cutpoint that defines prolonged intubation.

The durations that define prolonged intubation vary widely across both the

intubation (Macewen, 1880; Vogelhut & Downs, 1979) and dysphagia literature

(Ajemian et al., 2001; de Larminat et al., 1995; Tolep et al., 1996). The earliest record of prolonged endotracheal intubation, published in 1880, included patients who were intubated for 24 hours or more (Macewen, 1880). In contrast, other authors have defined prolonged intubation as greater than seven days (Vogelhut & Downs, 1979). In the dysphagia literature, prolonged intubation has been defined as greater than 24 hours (de

Larminat et al., 1995), 48 hours (Ajemian et al., 2001; Barker et al., 2009; Barquist et al.,

INTRODUCTION 33

2001; Bordon et al., 2011; Brodsky et al., 2014; El Solh et al., 2003; Leder, Cohn, et al.,

1998; Padovani et al., 2008) or 8 days (Tolep et al., 1996). This lack of consistency

makes comparisons across studies difficult.

Upper aerodigestive tract morbidities. Regardless of the medical necessity that

precipitated the need for endotracheal intubation, injuries to the upper aerodigestive tract

following endotracheal tube placement are recognized complications (Cook, Scott, &

Mihai, 2010; Domino, Posner, Caplan, & Cheney, 1999). Injuries to the larynx and

pharynx following endotracheal intubation account for over half of all closed anesthesia

claims in the US (Domino et al., 1999). Post-extubation upper aerodigestive tract

morbidities include structural and sensory changes which can lead to biomechanical

alterations that disrupt the structural coordination necessary for deglutition and airway

protection (Burns, Dayal, Scott, van Nostrand, & Bryce, 1979; DeVita & Spierer-

Rundback, 1990; El Solh et al., 2003; Medda et al., 2003; Santos, Afrassiabi, &

Weymuller, 1994; Sellery, Worth, & Greenway, 1978).

Injury and biomechanical changes. Nearly all intubated patients experience some degree of pharyngeal, laryngeal and/or subglottal damage (Colice, Stukel, & Dain, 1989;

Santos et al., 1994; Stauffer, Olson, & Petty, 1981; Thomas et al., 1995), which

ultimately affects glottal competence and airway protection. Clinically observable

symptoms range from mild cases of vocal hoarseness to more serious complications

including aphonia (Hamdan, Sibai, Rameh, & Kanazeh, 2007; Santos et al., 1994) and

stridor (Grillo, 1979; Grillo & Donahue, 1996; Macchiarini, Verhoye, Chapelier, Fadel,

& Dartevelle, 2001; Tadié et al., 2010). Post-extubation stridor as a result of inadequate

glottal opening can be potentially fatal precipitating the need for reintubation (Tadié et

al., 2010) and/or surgical intervention either by way of an emergent tracheotomy or

INTRODUCTION 34

surgical repair (Grillo, 1979; Grillo & Donahue, 1996; Macchiarini et al., 2001). Other

post-extubation vocal fold pathologies include: arytenoid subluxation (Talmi, Wolf, Bar-

Ziv, Nusem-Horowitz, & Kronenberg, 1996), edema, ulceration (Burns et al., 1979;

Colice et al., 1989; Santos et al., 1994; Tadié et al., 2010), tissue granulation (Colice et

al., 1989; Colton House, Noordzij, Murgia, & Langmore, 2011; Lundy, Casiano, Shatz,

Reisberg, & Xue, 1998; Mencke et al., 2003; Santos et al., 1994; Tadié et al., 2010),

abnormal vocal fold mobility (Burns et al., 1979; Colton House et al., 2011; Lundy et al.,

1998; Peppard & Dickens, 1983; Santos et al., 1994; Tadié et al., 2010), and vocal fold

hematomas (Mencke et al., 2003; Peppard & Dickens, 1983). Increased swelling

throughout the oropharynx may also occur, negatively affecting respiration by increased

laryngeal resistance (Tanaka, Isono, Ishikawa, Sato, & Nishino, 2003) and/or work of

breathing (Ishaaya, Nathan, & Belman, 1995). This edema may also affect swallowing

sensory integration due to the high density of afferent receptors throughout the area

including the pharyngeal mucosa, base of tongue and faucial pillars (DeVita & Spierer-

Rundback, 1990; Miller, 1982). Resolution of some LP injuries may occur in the weeks

following extubation (Colice, 1992; Colice et al., 1989; Peppard & Dickens, 1983; Santos

et al., 1994), with others having delayed onset and a more protracted recovery course

(Santos et al., 1994). As a result, LP injuries can affect the integrity of the swallow at

any time following extubation.

To our knowledge, only one study has evaluated the relation between intubation

duration and the co-occurrence of dysphagia and LP abnormalities (Postma et al., 2007).

The authors retrospectively evaluated the FEES examinations of 100 hospitalized patients

referred for swallowing assessments. They found a high incidence of glottal edema

(33%), granuloma formation (31%), and vocal fold paresis (24%) in those patients with

INTRODUCTION 35 dysphagia. While those who were intubated had significantly higher incidence of LP anomalies, nearly two thirds of the cohort who were not intubated also presented LP anomalies, thus, highlighting the importance of structural integrity for adequate swallowing mechanics.

Injury etiology. The etiologies of LP morbidities following intubation are typically mechanical in nature (Arts, Rettig, de Vries, Wolfs, & in't Veld, 2013; Combes et al., 2001; Dubick & Wright, 1978; Grillo, 1979; Grillo & Donahue, 1996; Hamdan et al., 2007; Honeybourne, Costello, & Barham, 1982; Lundy et al., 1998; Macchiarini,

Verhoye, Chapelier, Fadel, & Dartevelle, 2000; Macchiarini et al., 2001; Stauffer et al.,

1981; Tanaka et al., 2003) and are not necessarily a result of traumatic, difficult (Asai,

Koga, & Vaughan, 1998) or prolonged intubations (Heffner, 2010; Lundy et al., 1998).

Though debated throughout the literature (Braz, Volney, Navarro, Braz, & Nakamura,

2004; Colton House et al., 2011), LP injury location and severity is often dependent upon an oral versus nasal approach (Dubick & Wright, 1978), endotracheal tube type (Tanaka et al., 2003), cuff volume (Combes et al., 2001; Honeybourne et al., 1982), and cuff pressure (Arts et al., 2013; Combes et al., 2001; Hamdan et al., 2007). For example, when comparing oral versus nasal intubation, the incidence of laryngeal morbidity such as impaired glottis closure, laryngeal edema and ulceration was higher with an oral approach (Dubick & Wright, 1978). Injuries related to cuff location and volume include subglottic stenosis and tracheoesophageal fistula (Grillo, 1979; Grillo & Donahue, 1996;

Lundy et al., 1998; Macchiarini et al., 2000, 2001; Stauffer et al., 1981).

The recurrent laryngeal nerve may be damaged due to intubation (Cavo, 1985;

Dimarakis & Protopapas, 2004; Gibbin & Egginton, 1981; Hamdan et al., 2002; Ishimoto et al., 2002; Shafei et al., 1997). More specifically, the anterior branch of the RLN can

INTRODUCTION 36

be injured due to the insertion or alternatively, the presence of the endotracheal tube

(Brandwein, Abramson, & Shikowitz, 1986; Itagaki et al., 2007; Myssiorek, 2004; Stout,

Bishop, Dwersteg, & Cullen, 1987). Injury severity is often related to endotracheal tube

cuff position, volume (Brandwein et al., 1986; Itagaki et al., 2007; Myssiorek, 2004;

Stout et al., 1987), size, or placement duration (Inada, Fujise, & Shingu, 1998; Itagaki et

al., 2007; Myssiorek, 2004; Stout et al., 1987). Kikura and colleagues (2006) reported a two-fold increase in the odds of vocal fold injury with intubations of three to six hours compared to a fifteen-fold increase in RLN injury in those patients intubated for 15 hours or more (Kikura, Suzuki, Itagaki, Takada, & Sato, 2007). As a result, those with postoperative vocal cord paralysis should be treated with an interdisciplinary approach and undergo early diagnosis and management in order to minimize post-operative complications (Schneider et al., 2003), such as dysphagia, which may contribute to respiratory decompensation or even death.

Mechanical ventilation and the swallow. Patients requiring mechanical ventilation comprise a diagnostic subgroup with a tenuous respiratory system and unique respiratory physiology (Aliverti et al., 2011; Blackwood et al., 2011; Capdevila et al.,

1998; Esteban et al., 2002; Habib, Zacharias, & Engoren, 1996; Herridge et al., 2011;

Ishaaya et al., 1995; Zhu, Lee, & Chee, 2012). Those requiring mechanical ventilation often need respiratory support due to pathological processes that decrease lung compliance, pulmonary elasticity and respiratory muscle strength as well as contribute to alveolar derecruitment and impaired muccociliary clearance (Ashbaugh, Bigelow, Petty,

& Levine, 1967; Crimi & Slutsky, 2004; Fan, Needham, & Stewart, 2005; Habib et al.,

1996; Petty & Ashbaugh, 1971; Zhu et al., 2012). Because of their underlying respiratory physiology, these patients are at an intrinsic disadvantage in their ability to overcome any

INTRODUCTION 37 respiratory complications secondary to dysphagia (Cvejic et al., 2011; Gross, Atwood,

Ross, Olszewski, & Eichhorn, 2009; Harding, 2002; Martin-Harris, Michel, & Castell,

2005; Nishino, 2012). When compared to other patient groups, the recently extubated patient differs in more ways. The decision to proceed with extubation is based on many clinical and pulmonary factors (Blackwood et al., 2011; Fan et al., 2005; Yang & Tobin,

1991) including breathing patterns, work of breathing and respiratory physiology

(Blackwood et al., 2011; Capdevila et al., 1998; Ishaaya et al., 1995; Khamiees, Raju,

DeGirolamo, Amoateng-Adjepong, & Manthous, 2001; Leitch, Moran, & Grealy, 1996;

Mehta, Nelson, Klinger, Buczko, & Levy, 2000). Although breathing patterns and respiratory function are often similar for patients both before and shortly following extubation, it differs from that of healthy subjects (Krieger, Chediak, Gazeroglu,

Bizousky, & Feinerman, 1988). As we will discuss in the subsequent sections, these respiratory variations from normal (Nishino, 2012) along with changes in the swallowing reflex and apneic period following mechanical ventilation (Hasegawa & Nishino, 1999), increases a patient’s risk for dysphagia and its sequelae (Martin, Logemann, et al., 1994;

Martin-Harris, Michel, et al., 2005; Nilsson, Ekberg, Bülow, & Hindfelt, 1997).

Breathing and swallowing: Taxing an already taxed system. Mechanical ventilation has an immediate and sometimes lasting effect on the coordination of swallowing and respiration (Elpern et al., 1994; Hasegawa & Nishino, 1999; Nishino,

2012; Nishino, Sugimori, Kohchi, & Hiraga, 1989). Abnormal breathe-swallow coordination has been observed in numerous patient populations (Hadjikoutis,

Pickersgill, Dawson, & Wiles, 2000; Hirst, Ford, Gibson, & Wilson, 2002; Nilsson et al.,

1997; Selley, Flack, Ellis, & Brooks, 1989b) including those following mechanical ventilation (Aliverti et al., 2011; Capdevila et al., 1998; Elpern et al., 1994; Hasegawa &

INTRODUCTION 38

Nishino, 1999; Nishino, 2012). This discoordination often increases the frequency of

airway penetration and/or aspiration (Nilsson et al., 1997) predisposing patients to

pulmonary complications (Martin, Logemann, et al., 1994; Martin-Harris, Michel, et al.,

2005). Healthy subjects enact a protective mechanism that involves a spontaneous phase resetting of the inhalation-exhalation respiratory pattern when they are about to engage in a swallowing act (Paydarfar, Gilbert, Poppel, & Nassab, 1995; Terzi et al., 2007).

Following mechanical ventilation, patients often initiate their swallow during inspiration

(Hadjikoutis et al., 2000; Nishino, 2012; Nishino & Hiraga, 1991) even though their breathe-swallow cycle still remains coupled (Nishino & Hiraga, 1991). In addition, their airway may be compromised further due to temporal and apneic period alterations during swallowing (Hasegawa & Nishino, 1999; Paydarfar et al., 1995).

Patients who are tachypneic, hypercapneic or hypoxemic are at increased risk of aspiration when compared to those who are not (Boden et al., 2009; Gross et al., 2009;

Matsuo, Hiiemae, Gonzalez-Fernandez, & Palmer, 2008; Nishino, Hasegawa, Ide, &

Isono, 1998). Following extubation, patients often exhibit compensatory respiratory mechanics as a result of their altered lung volumes (Habib et al., 1996; Zhu et al., 2012) leading to increased work of breathing and respiratory rates (Ishaaya et al., 1995; Mehta et al., 2000). These increases can result in a shortening of the obligatory apneic period during swallowing (Boden et al., 2009; Martin, Logemann, et al., 1994; Nilsson et al.,

1997; Nishino et al., 1998). In addition, these patients may also engage in suboptimal ventilation (Blackwood et al., 2011; Habib et al., 1996; Zhu et al., 2012). The net effect of these respiratory alterations results in decreased glottic closure durations with a higher likelihood of an unprotected airway while the bolus passes through the pharynx (Boden et al., 2009; Gross, Atwood, Grayhack, & Shaiman, 2003; Nishino et al., 1998).

INTRODUCTION 39

Altered respiratory physiology and its adverse effect on the swallow has also been demonstrated in healthy subjects (Gross et al., 2003; Nishino et al., 1998). In an experimental paradigm illustrating the effect of altered lung volumes, healthy subjects with normal swallows were given oral trials at three randomized and artificially-induced lung volumes: total lung capacity, function residual capacity and residual volume (Gross et al., 2003). The duration of pharyngeal activity was significantly shorter in the latter two lung volume paradigms with more frequent airway compromise (Gross et al., 2003).

Similar findings were reported in an earlier study (Nishino et al., 1998). When

hypercapnea was induced, the subjects’ swallowing rate decreased, breathing and

swallowing became discoordinated, and swallow timing was altered (Nishino et al.,

1998). The hypercapneic condition induced more frequent clinical instances of aspiration

and those who exhibiting these clinical signs, often initiated swallowing during the

inhalatory phase (Nishino et al., 1998). Throughout the study, no clinical instances of

aspiration occurred during the expiratory phase (Nishino et al., 1998). These studies

support the premise that although recently extubated patients are able to sustain

respiration unsupported, their dysphagia risk is greater than that of healthy subjects for

numerous reasons including an inability to sustain adequate airway protection during

swallowing due to alterations with their: respiratory pattern, breathe-swallow coordination, respiratory rate and the timing of swallowing activities.

Anesthesia and upper aerodigestive function. Drug regimens utilized for

general anesthesia can have a sedating and lasting effect (Chia, Lee, & Liu, 2008;

d'Honneur et al., 1992; Isono, Ide, Kochi, Mizuguchi, & Nishino, 1991; Mencke et al.,

2014; Nishino & Hiraga, 1991; Park et al., 2011; Rimaniol, D'Honneur, & Duvaldestin,

1994; Sauer, Stahn, Soltesz, Noeldge-Schomburg, & Mencke, 2011) impairing airway

INTRODUCTION 40 protection capabilities (Cedborg et al., 2014; Chia et al., 2008; Isono et al., 1991; Mencke et al., 2003; Sundman et al., 2001). Although these regimens minimize upper airway complications by allowing for ease of intubation, subsequent induction and eventual extubation (Chia et al., 2008; Honarmand & Safavi, 2008; Mazzarella et al., 1987;

Mencke et al., 2014; Park et al., 2011), higher frequencies of LP impairments have been reported with some drug regimens when compared to others (Mencke et al., 2006) along with lasting laryngeal effects even after reversal (Sauer et al., 2011). In healthy volunteers, Sundman and colleagues (2001) evaluated the effect of various anesthesia medications on airway competence while assessing swallowing with videoradiography and pharyngeal manometry (Sundman et al., 2001). Airway penetration and impaired pharyngeal constriction persisted even as subhypnotic doses of propofol, isoflurane or sevoflurane were weaned and/or reversed (Sundman et al., 2001). Similarly, in another study with healthy subjects, swallowing became progressively impaired with decreased airway protection during partial neuromuscular blockade (Cedborg et al., 2014). While the half-life and residual effects of many anesthesia medications are relatively short ranging from 20 minutes to approximately two hours (d'Honneur et al., 1992; d'Honneur et al., 1996), the effect of anesthesia can be unique and longer lasting in various muscle groups (d'Honneur et al., 1992; d'Honneur et al., 1996; Hwang, St John, & Bartlett, 1983;

Nishino, Shirahata, Yonezawa, & Honda, 1984).

Some induction medications have a more pronounced effect on upper aerodigestive musculature (d'Honneur et al., 1996). Those muscles involved in swallowing and airway patency recover more slowly following induction when compared to those involved in respiration (d'Honneur et al., 1996; Hwang et al., 1983; Nishino et al., 1984). For example, in animal studies the cranial nerve (CN) that innervates the

INTRODUCTION 41 intrinsic lingual muscles (CN XII) is more sensitive to general anesthetics than the vagus and phrenic nerves (Hwang et al., 1983; Nishino et al., 1984). The recovery time of laryngeal muscles following anesthesia also differs when compared to those in the hand

(Donati, Meistelman, & Plaud, 1991; Plaud, Debaene, Lequeau, Meistelman, & Donati,

1996). This differential sensitivity and recovery time is of particular importance during the period following anesthesia and extubation (Isono et al., 1991). Oral feeding is typically considered at this time as the patient is breathing spontaneously; however, swallowing can be impaired following anesthesia even if respiration is unassisted

(Cedborg et al., 2014; Isono et al., 1991). As a result, it is still not clear when oral feeding can be initiated following extubation (Kerz & Wahlen, 2004).

INTRODUCTION 42

III. Cardiovascular Surgery

Heart Disease

Burden of care. Approximately 1.3 million Canadians have heart disease (Heart

and Stroke Foundation of Canada, 2003; Lee et al., 2009; Public Health Agency of

Canada, 2009). Heart disease accounts for 20% of all Canadian hospitalizations and is

the leading cause of death in Canada (Heart and Stroke Foundation of Canada, 2003; Lee

et al., 2009; Public Health Agency of Canada, 2009). In 2000, cardiovascular disease incurred over $22 billion in costs to the Canadian healthcare system (Heart and Stroke

Foundation of Canada, 2003; Public Health Agency of Canada, 2009) and continues to impart substantial economic burden by incurring millions of dollars in long-term

disability annually (Heart and Stroke Foundation of Canada, 2003). At a cost of $3,400

per patient per hospitalization (Heart and Stroke Foundation of Canada, 2003; Public

Health Agency of Canada, 2009), heart disease-related hospital admissions are the highest incurring cost category across all medical diagnoses (Heart and Stroke

Foundation of Canada, 2003; Public Health Agency of Canada, 2009). While the

mortality rate for all cardiovascular diseases dropped by 56% between the years of 1969-

1999 and continues to do so (Heart and Stroke Foundation of Canada, 2003), heart

disease prevalence is rising with nearly 40% of adults having three or more of its risk

factors (Public Health Agency of Canada, 2009).

Heart disease risk factors. Heart disease risk factors differ for coronary vessel

and valve disease. Risk factors for vessel disease are primarily attributed to remediable

lifestyle or environmental factors (Greenland et al., 2003; Heart and Stroke Foundation of

Canada, 2003; Public Health Agency of Canada, 2009; Rosengren et al., 2004; Yusuf et

al., 2005; Yusuf et al., 2004). The large INTERHEART study, including 226 coronary

INTRODUCTION 43 care facilities across 52 countries, identified a risk factor set that was attributable for 90% of coronary vessel disease (Yusuf et al., 2004). These lifestyle or environmental related factors included: abnormal lipids, smoking, hypertension, diabetes, abdominal obesity

(Yusuf et al., 2005; Yusuf et al., 2004), psychosocial factors (i.e., a combination of home, work related or financial stresses and/or anxiety and/or depression) (Rosengren et al.,

2004; Yusuf et al., 2004), limited consumption of fruits and vegetables, regular consumption of alcohol, and limited physical activity (Yusuf et al., 2005; Yusuf et al.,

2004). Risk factors for cardiac valve dysfunction include congenital anomalies, systemic disease and/or degenerative processes (Bakir, Onan, Onan, Gul, & Uslu, 2013; Bolling et al., 2010; Boudoulas et al., 2013; David, Armstrong, McCrindle, & Manlhiot, 2013;

David, Ivanov, Armstrong, Christie, & Rakowski, 2005; Lio et al., 2014; Modi, Hassan,

& Chitwood, 2008; Rankin et al., 2013) for example; endocarditis, rheumatic heart disease (Bakir et al., 2013; Boudoulas et al., 2013; Yau, El-Ghoneimi, Armstrong,

Ivanov, & David, 2000), and myocardial ischemia (Boudoulas et al., 2013; Lio et al.,

2014; Rankin et al., 2013). When medical management is no longer sufficient for remediating cardiac-related illnesses, cardiovascular surgery is often required (Heart and

Stroke Foundation of Canada, 2003; Public Health Agency of Canada, 2009).

Cardiovascular Surgery Types

In 2005 alone, over 32,000 coronary artery bypass and/or heart valve surgeries were performed in Canada (Heart and Stroke Foundation of Canada, 2003; Public Health

Agency of Canada, 2009). The most frequent age demographic undergoing valve and/or bypass surgery were patients between 65-80 years of age (Heart and Stroke Foundation of Canada, 2003; Public Health Agency of Canada, 2009). Across all hospitalizations in the US, coronary artery bypass grafting and cardiac valve surgery is the most common

INTRODUCTION 44

surgical intervention with total hospital costs ranging from $7, 054 to $46, 317 per patient

(Kilic et al., 2014).

Cardiovascular surgeries, including coronary artery bypass and/or valve surgery, are life sustaining procedures given the roles of the heart, major coronary arteries and the tricuspid, mitral, pulmonic and aortic valves (Hillis et al., 2011; Nishimura et al., 2014).

Coronary arteries supply the myocardium with blood (Hillis et al., 2011) while the

cardiac valves aid in the prevention of regurgitant blood flow throughout the heart

chambers (Nishimura et al., 2014). Coronary artery bypass grafting is a surgical

procedure where one or multiple constricted coronary arteries are bypassed using

autologous arteries or veins serving to improve blood supply to the myocardium (Hillis et

al., 2011). In 1960, the first successful bypass procedure was performed by Dr. Goetz in

the US (Goetz, Rohman, Haller, Dee, & Rosenak, 1961). Subsequently in 1964, Dr.

Kolesov completed the first successful bypass using a suture closure in Russia (Kolesov

& Potashov, 1965). Either with or without coronary artery bypass grafting, cardiac valve

surgery consists of repair or replacement of any of the one or more heart valves

(Boudoulas et al., 2013; Nishimura et al., 2014). Cardiac valves are repaired or replaced

if they have a primary congenital pathology (Sarris, Comas, Tobota, & Maruszewski,

2012) or exhibit either regurgitation or stenosis (Bakir et al., 2013; Boodhwani & El

Khoury, 2014; David et al., 2013; Nishimura et al., 2014; Yau et al., 2000). Valve

surgery can include either the rebuilding or reshaping of a valve leaflet (annuloplasty) or

a complete valve replacement with a mechanical or biological valve (Bolling et al., 2010;

Boodhwani & El Khoury, 2014; David et al., 2013; David, Bos, & Rakowski, 1992;

David et al., 2005; Denti, Maisano, & Alfieri, 2014; Nishimura et al., 2014).

INTRODUCTION 45

These cardiac surgeries can be conventional (Hillis et al., 2011; Nishimura et al.,

2014), minimally invasive (Bravata et al., 2007; Cheng et al., 2011; Modi et al., 2008;

Rosengart et al., 2008) and/or robot-assisted (Chitwood et al., 2008; Mohr, Falk,

Diegeler, & Autschback, 1999). Often, the method that is utilized dependent on numerous surgical, medical and patient variables (Boodhwani & El Khoury, 2014;

Bravata et al., 2007; David et al., 2013; David et al., 2005; Hillis et al., 2011; Liebrich et

al., 2013; Nishimura et al., 2014; Ralph-Edwards, Robinson, Gordon, & Ivanov, 1999).

Although the medical outcomes (Bravata et al., 2007; Hill et al., 2004; Ivanov, Borger,

Tu, Rao, & David, 2008; Modi et al., 2009; Wan et al., 2013) and cost efficiency of

newer approaches are continuously debated (Awad, Mathur, Baldock, Oliver, & Kennon,

2014; Hill et al., 2004; Sellke et al., 2005; Vassileva et al., 2013), the evolution of CV

surgery to include off-pump procedures (Sedrakyan, Wu, Parashar, Bass, & Treasure,

2006) or minimally invasive interventions (Bravata et al., 2007; Cheng et al., 2011; Modi

et al., 2008) have resulted in favorable clinical outcomes with a reduction in adverse

events for some populations. Fortunately these and other modern surgical approaches

have resulted in declining mortality rates (Cheng et al., 2011; Heart and Stroke

Foundation of Canada, 2003; Ivanov et al., 2008; Liebrich et al., 2013; Modi et al., 2008;

Public Health Agency of Canada, 2009); however, as the number of survivors increase so

does the risk and frequency of post-operative morbidities (David et al., 2013; Ralph-

Edwards et al., 1999; Rao et al., 1996; Song et al., 2009; Takagi, Tanabashi, Kawai, &

Umemoto, 2007).

Risk Factors for Dysphagia Following CV Surgery

The manifestation of dysphagia following CV surgery has been associated with

surgical, medical and patient-specific factors (Burgess et al., 1979; Ferraris et al., 2001;

INTRODUCTION 46

Hogue et al., 1995; Messina et al., 1991; Partik et al., 2003; Rousou et al., 2000). Across

the CV surgical population, the incidence of dysphagia approximates 3-4% (Ferraris et

al., 2001; Hogue et al., 1995; Rousou et al., 2000). Following intubation durations of

greater than 48 hours, the frequency increases to approximately 51% (Barker et al.,

2009). Other risk factors for dysphagia include surgery type (Barker et al., 2009; Ferraris

et al., 2001), peri-operative TEE use (Hogue et al., 1995; Rousou et al., 2000), operative time (Rousou et al., 2000), age (Ferraris et al., 2001; Harrington et al., 1998; Hogue et al.,

1995) and vocal fold immobility (Joo, Duarte, Ghadiali, & Chhetri, 2009). However,

their association with dysphagia is not consistently supported in the literature (Hogue et

al., 1995; Messina et al., 1991; Rousou et al., 2000). It is yet unknown whether the

discrepancies in these reported risks are due to differences in study design and/or

methodological quality.

Surgery type. Patients undergoing valve surgery reportedly experience post-

operative dysphagia more frequently as compared to patients undergoing other cardiac

procedures (Barker et al., 2009; Ferraris et al., 2001), however, this finding is not

consistent (Hogue et al., 1995; Rousou et al., 2000). To date, no study has evaluated the

impact of surgical methods on swallowing physiology therefore; the biological

plausibility underlying the higher incidence of dysphagia following valvular surgery is

still unknown.

Transesophageal echocardiogram. Transesophageal echocardiogram (TEE), a

cardiac imaging tool which aids in surgical and clinical decision-making, is used intra- operatively as a means for gathering real-time anatomic and physiological information regarding cardiac function, valvular competence, and arterial patency (Bergquist,

Bellows, & Leung, 1996; Bergquist, Leung, & Bellows, 1996; Eltzschig et al., 2008;

INTRODUCTION 47

Enriquez-Sarano et al., 1999; Kihara et al., 2009; le Polain de Waroux et al., 2007; Van

Dyck, Watremez, Boodhwani, Vanoverschelde, & El Khoury, 2010). Operative

outcomes are improved with the use of TEE (Bergquist, Bellows, et al., 1996; Bergquist,

Leung, et al., 1996; Enriquez-Sarano et al., 1999; le Polain de Waroux et al., 2007; Van

Dyck et al., 2010) and TEE-associated morbidities or mortalities are rare <0.2% (Daniel et al., 1991; Kallmeyer, Collard, Fox, Body, & Shernan, 2001; Min et al., 2005; Piercy,

McNicol, Dinh, Story, & Smith, 2009).

The peri-operative TEE probe is passed through the pharynx, the esophagus and into the stomach and as a result, adverse events may include complications to the upper aerodigestive tract (Côté & Denault, 2008; Daniel et al., 1991; Owall, Ståhl, &

Settergren, 1992; Piercy et al., 2009). A systematic review on transesophageal-related

complications by Cote and colleagues (2008) identified primary regions for these

complications including: oropharyngeal (odynophagia, dental injury, vocal fold paralysis,

dysphagia), pulmonary (bronchospasm, endotracheal tube malposition) and upper

gastrointestinal (GI) (upper GI hemorrhage, esophageal abrasion, esophageal perforation

(Côté & Denault, 2008). Although these regions are intrinsic in the execution of a safe

swallow, the occurrence of TEE-related swallowing morbidity is rare (Kallmeyer et al.,

2001). For example, in a study of 7200 TEE cases (Kallmeyer et al., 2001), the incidence

of swallowing related post-operative morbidity was small: odynophagia (.1%), dysphagia

(.01%), esophageal abrasions (.06%) and dental injury (.03%).

Despite the rare occurrence of TEE-related dysphagia, TEE use has been reported

as an independent predictor of the disorder (Hogue et al., 1995; Rousou et al., 2000).

Due to the location of the TEE probe intra-operatively, some authors have suggested that post-TEE dysphagia is secondary to RLN injury (Sakai et al., 1999). Sakai and

INTRODUCTION 48

colleagues (1999) reported significantly greater post-TEE RLN palsy occurring in

females as compared to males (Sakai et al., 1999). This finding has been corroborated by

other others (Piercy et al., 2009) suggesting that the smaller female upper aerodigestive

tract is at greater risk of compression-related injuries. However, contradictory findings

have also been published (Kawahito, Kitahata, Kimura, Tanaka, & Oshita, 1999; Messina

et al., 1991; Owall et al., 1992). In a study comparing RLN injury and TEE usage, no

significant differences between sexes were noted (Kawahito et al., 1999). Rather than

TEE, these authors implicated surgery type, surgical time and intubation duration as

predictive factors in RLN injury (Kawahito et al., 1999). Patients requiring prolonged

TEE often have more severe illness and require prolonged surgical times (Hogue et al.,

1995), thereby confounding the relation between TEE use and dysphagia.

Cardiopulmonary bypass. Conventional cardiopulmonary bypass (CPB), or extracorporeal circulation, is a peri-operative necessity for many cardiovascular surgeries; however, due to its unnatural processes which include the exposure of blood elements to nonintimal structures, nonpulsatile flow, abnormal homeostasis and increased coagulation activation, its use often precipitates and/or compounds the patient’s

protective inflammatory response (Laffey, Boylan & Cheng, 2002; Warren et al.,2009).

These inflammatory responses manifest clinically in many ways including neurological

morbidity (Lee et al., 2003; Lev-Ran et al., 2005; Mack et al., 2004), stroke (Borger et

al., 1998; Borger, Ivanov, Weisel, Rao, & Peniston, 2001; Hogue, Murphy, Schechtman,

& Dávila-Román, 1999; Likosky et al., 2003; Rao et al., 1995) and/or neurocognitive

deficits (Djaiani et al., 2004; Doganci, Gunaydin, Kocak, Yilmaz, & Demirkilic, 2013;

Floyd et al., 2006; Newman et al., 2001; Zanatta et al., 2013) . Nissinen and colleagues

(2009) evaluated the impact of cardiopulmonary bypass duration along with aortic cross-

INTRODUCTION 49

clamp time during cardiovascular surgery. They reported that increasing time intervals of

both aortic cross clamping and cardiopulmonary bypass increased the odds of post-

operative morbidity, particularly stroke, by 1.2 and 1.5 respectively (Nissinen, 2009).

Stroke. While majority of patients with stroke have dysphagia irrespective of other medical comorbidities (Martino et al., 2005), stroke following CV surgery is a rare occurrence ranging from 1.3% - 4.6% (Borger et al., 2001; Bucerius et al., 2003; Hogue et al., 1999; Likosky et al., 2003; Salazar et al., 2001). Despite this, overall patient outcomes associated with stroke following CV surgery are significantly poorer than those without stroke with the majority of patients facing long-term moderate to severe deficits along with lower survival rates at one and five years post-surgery (Salazar et al., 2001).

Risk factors for peri-operative stroke include age (Rao et al., 1995), pre-operative stroke

(Bucerius et al., 2003; Rao et al., 1995; Ricotta, Faggioli, Castilone, & Hassett, 1995), carotid stenosis >50%, reoperation, cardiopulmonary bypass and valve surgery (Bucerius et al., 2003; Ricotta et al., 1995). While the majority of those with stroke have dysphagia

(Martino et al., 2005), only one study has reported stroke as an independent predictor of dysphagia following CV surgery (Rousou et al., 2000). Others have reported that neither pre- nor peri-operative strokes are associated with its development (Barker et al., 2009;

Ferraris et al., 2001; Hogue et al., 1995).

Recurrent laryngeal nerve injury. Recurrent laryngeal nerve injury is a known outcome secondary to both heart disease (Camishion, Gibbon, & Pierucci, 1966; Morgan

& Mourant, 1980; Victoria, Graham, Karnell, & Hoffman, 1999) as well as cardiovascular surgery (Benouaich et al., 2012; Dimarakis & Protopapas, 2004; Hamdan et al., 2002; Ishimoto et al., 2002; Murty & Smith, 1989; Myssiorek, 2004; Tewari &

Aggarwal, 1996). The frequency of vocal fold immobility, either unilateral or bilateral

INTRODUCTION 50 paralysis or paresis, following CV surgery is rare <2% (Dimarakis & Protopapas, 2004;

Itagaki et al., 2007; Shafei et al., 1997) however this post-operative outcome can greatly reduce a patient’s quality of life (Zumtobel, End, Bigenzahn, Klepetko, & Schneider,

2006) and increase their dysphagia risk (Joo et al., 2009; Leder & Ross, 2005; Leder,

Suiter, Duffey, & Judson, 2012; Rosenthal, Benninger, & Deeb, 2007). Recovery of the

RLN injury depends upon the rate of axonal neuroregeneration as well as the etiology of the RLN injury (Zealear & Billante, 2004). The injury, regardless of etiology, may be temporary, resolving within 6 months following surgery (Joo et al., 2009) or take longer to recover if at all (Ishimoto et al., 2002).

In both non-surgical and surgical cardiac patients, the etiology and severity of

RLN injury depends on anatomical, mechanical and surgical variables (Camishion et al.,

1966; Morgan & Mourant, 1980; Victoria et al., 1999). In patients with heart disease, the

RLN may be injured by way of compression secondary to an enlarged left atrium

(Camishion et al., 1966; Morgan & Mourant, 1980). In rare cases, RLN injury occurs following cardioversion for atrial fibrillation (Victoria et al., 1999). Due to the aortic and subclavian course of the RLN (Benouaich et al., 2012), injury may occur due to sternotomy, sternal retraction and the mediastinal operating site location (Benouaich et al., 2012; Dimarakis & Protopapas, 2004; Murty & Smith, 1989; Myssiorek, 2004;

Tewari & Aggarwal, 1996). Intra-operative factors potentially causing RLN damage include myocardial cooling (Dimarakis & Protopapas, 2004; Hamdan et al., 2002; Tewari

& Aggarwal, 1996), aortic manipulation (Ishimoto et al., 2002; Itagaki et al., 2007), and central venous catheterization (Martin-Hirsch & Newbegin, 1995). Etiology notwithstanding, patients with post-operative vocal fold immobility present a diagnostic

INTRODUCTION 51 subgroup at increased risk for dysphagia (Joo et al., 2009; Leder et al., 2012; Rosenthal et al., 2007).

Post-operative vocal fold immobility increases a patient’s risk of dysphagia primarily due to airway protection impairment (Leder & Ross, 2005; Leder et al., 2012;

Rosenthal et al., 2007). This may contribute to respiratory morbidity (Leder & Ross,

2005; Leder et al., 2012; Rosenthal et al., 2007) and even death (Cavo, 1985; Gibbin &

Egginton, 1981). In a retrospective cohort study, all patients with either unilateral or bilateral vocal fold paralysis following CV surgery exhibited hoarseness, weak cough and dysphagia for thin fluids (Joo et al., 2009). In another study exploring vocal fold immobility across hospitalized patients, over a third of the patients exhibited airway penetration with nearly a quarter exhibiting aspiration (Bhattacharyya et al., 2003).

Prolonged intubation following cardiovascular surgery. All patients undergoing cardiovascular (CV) surgery require endotracheal intubation and mechanical ventilation as part of standard surgical intervention; however, the duration of intubation after surgery varies (Cislaghi, Condemi, & Corona, 2009; Reddy, Grayson, Griffiths,

Pullan, & Rashid, 2007). Fast-tracked extubation, which is typically defined as extubation within six to eight hours post-operatively (Cheng, 1998), is now considered standard care worldwide (Silbert & Myles, 2009; Zhu et al., 2012). Historically, the duration that defined a fast-tracked extubation was reportedly arbitrary with no physiological basis (Zhu et al., 2012). This fast-tracking however has resulted in improved patient outcomes, including improved respiratory and circulatory outcomes

(Cheng et al., 1996; Ingersoll & Grippi, 1991) and a marked reduction in hospitalization costs (Arom, Emery, Petersen, & Schwartz, 1995; Cheng, 1998; Hawkes, Dhileepan, &

Foxcroft, 2003; Rashid, Sattar, Dar, & Khan, 2008).

INTRODUCTION 52

Similar to the time period that defines early or fast-tracked extubation following

CV surgery (Zhu et al., 2012), the intubation period that constitutes a prolonged duration

is also arbitrary (Cheng et al., 1996; Christian, Engel, & Smith, 2011; Cislaghi et al.,

2009; Cohen et al., 2000; Habib et al., 1996; Légaré, Hirsch, Buth, MacDougall, &

Sullivan, 2001; Pappalardo et al., 2004; Reddy et al., 2007; Trouillet et al., 2009;

Widyastuti, Stenseth, Pleym, Wahba, & Videm, 2012; Yende & Wunderink, 2002). In the CV surgery literature, prolonged intubation has been defined as greater than: eight hours (Yende & Wunderink, 2002); 12 hours (Cheng et al., 1996; Cislaghi et al., 2009),

24 hours (Habib et al., 1996; Légaré et al., 2001; Widyastuti et al., 2012), 48 hours

(Cohen et al., 2000; Reddy et al., 2007), 72 hours (Christian et al., 2011; Trouillet et al.,

2009), seven days (Pappalardo et al., 2004) or 14 days (Combes et al., 2003). The dysphagia literature is similarly inconsistent with prolonged intubations defined as greater than: 24 hours (de Larminat et al., 1995), 48 hours (Ajemian et al., 2001; Barker et al., 2009; El Solh et al., 2003; Leder, Cohn, et al., 1998) or eight days (Tolep et al.,

1996). Regardless of these cutpoints, ultimately the patient’s medical status determines how long endotracheal intubation and mechanical ventilation are needed (Branca,

McGaw, & Light, 2001; Christian et al., 2011; Cislaghi et al., 2009; Habib et al., 1996; Ji et al., 2010; Légaré et al., 2001; Reddy et al., 2007; Suematsu et al., 2000; Widyastuti et al., 2012; Yende & Wunderink, 2002).

Prolonged intubation has been consistently reported as an independent predictor of dysphagia following CV surgery (Barker et al., 2009; Hogue et al., 1995; Rousou et al., 2000). When compared to the overall incidence of dysphagia (approximately 3%)

following CV surgery using cumulative intubations across the sample (Ferraris et al.,

2001; Hogue et al., 1995; Rousou et al., 2000), the frequency of dysphagia increases over

INTRODUCTION 53 ten-fold following durations exceeding 48 hours to approximately 51% (Barker et al.,

2009). While relatively few studies have reported on dysphagia following CV surgery

(Barker et al., 2009; Burgess et al., 1979; Ferraris et al., 2001; Harrington et al., 1998;

Hogue et al., 1995; Messina et al., 1991; Partik et al., 2003; Rousou et al., 2000), most report cumulative dysphagia frequencies regardless of intubation duration (Ferraris et al.,

2001; Hogue et al., 1995; Rousou et al., 2000), with only two (Barker et al., 2009;

Burgess et al., 1979) focusing on specific intubation times: greater than 48 hours (Barker et al., 2009) and from eight to 28 hours (Burgess et al., 1979). As a result, dysphagia frequencies following durations of less than 24 hours or between 24 to 48 hours are unknown providing uncertainty as to which patients are at the greatest risk.

Age. Age itself is an independent predictor of dysphagia following CV surgery

(Barker et al., 2009; Hogue et al., 1995); however, it remains to be determined if advanced age alone or the combination of age and other age-associated post-operative morbidities are causative factors in the development of dysphagia. According to the

United Nations report on World Aging published in 2013, by the year 2050, there will be

2 billion people worldwide over the age of 60 as compared to 841 million in 2013

(United Nations, 2013). Due to the effects of aging and degenerative disease processes on the cardiovascular system, this will increase the need for cardiac interventions exponentially (Ferrari, Radaelli, & Centola, 2003; Scott, Seifert, Grimson, & Glass,

2005). While the elderly population has similar outcomes for isolated cardiac interventions when compared to a younger cohort (Vasques, Messori, Lucenteforte, &

Biancari, 2012), age in itself remains a risk for significant post-operative morbidities

(Barnett et al., 2003; Fremes et al., 1989; Scott et al., 2005; Vasques, Lucenteforte,

Paone, Mugelli, & Biancari, 2012), which may increase a patient’s risk for dysphagia.

INTRODUCTION 54

As patients age, surgeries are often more complex requiring multiple interventions, prolonged aortic cross clamp time and therefore prolonged CPB (Tjang, van Hees,

Körfer, Grobbee, & van der Heijden, 2007; Vasques, Lucenteforte, et al., 2012). As a result, the elderly face an increased risk of reperfusion injury, systemic inflammatory response (Cremer et al., 1996; Nissinen et al., 2009) and microemboli (Djaiani et al.,

2004; Doganci et al., 2013; Floyd et al., 2006; Zanatta et al., 2013). The elderly have higher rates of post-operative stroke (Vasques, Lucenteforte, et al., 2012), longer durations of endotracheal intubation (Barnett et al., 2003; Scott et al., 2005), and death

(Barnett et al., 2003; Fremes et al., 1989; Tjang et al., 2007; Vasques, Lucenteforte, et al.,

2012).

Dysphagia Characteristics

Dysphagia has been characterized following CV surgery primarily through case studies (Adkins, Maples, Graham, Witt, & Davies, 1986; Cappell, 1991, 1995; Chesshyre

& Braimbridge, 1971; Dines & Anderson, 1966; Galvin et al., 1988; Morgan & Mourant,

1980; Skoretz & Rebeyka, 2009; Skoretz et al., 2012; Tekin et al., 2000). Only two studies with samples greater than ten have provided more extensive dysphagia descriptions following CV surgery (Hogue et al., 1995; Partik et al., 2003). All case studies but two (Skoretz & Rebeyka, 2009; Skoretz et al., 2012) describe the dysphagia as primarily esophageal as a result of cardiac-related esophageal compression (Cappell,

1991; Chesshyre & Braimbridge, 1971; Dines & Anderson, 1966; Morgan & Mourant,

1980; Tekin et al., 2000). One case series including only adults with aortic arch malformations described general oropharyngeal dysphagia signs and symptoms (Adkins et al., 1986). All but four studies (Hogue et al., 1995; Partik et al., 2003; Skoretz &

Rebeyka, 2009; Skoretz et al., 2012), two case studies (Skoretz & Rebeyka, 2009;

INTRODUCTION 55

Skoretz et al., 2012) and two with larger samples (Hogue et al., 1995; Partik et al., 2003),

described dysphagia using diagnostic methods ill-equipped to assess both oral and

pharyngeal aspects of the swallow.

The four studies, which described oral and pharyngeal aspects of the swallow following CV surgery, utilized radiographic methods specifically developed to assess dysphagia including barium cineradiography (Hogue et al., 1995) and videofluoroscopy

(Partik et al., 2003; Skoretz & Rebeyka, 2009; Skoretz et al., 2012). In both case studies,

Skoretz and colleagues described the swallowing impairments as primarily pharyngeal in

nature with airway compromise characterized by both penetration and aspiration (Skoretz

& Rebeyka, 2009; Skoretz et al., 2012). Hogue and colleagues (1995) confirmed

dysphagia in 4% (n=34, N=869) of their patients and reported on a variety of oral and

pharyngeal functions. Neither the case studies nor the study by Hogue and colleagues

provided operational definitions of the swallowing impairment. In contrast, Partik and

colleagues (2003) enrolled a mixed pediatric and adult symptomatic patient sample

(N=22). They described the swallowing function using operationally defined

terminology for various oral and pharyngeal aspects. While these studies are the first to

provide some characterization of the swallowing impairment following CV surgery, no

study to date has analyzed swallowing physiology following CV surgery using

standardized rating scales or objective physiological measurements. As a result, the

mechanisms underlying dysphagia in this population are largely undetermined as are the

best methods by which to assess and treat the disorder.

Gaps in the Literature

The frequency of dysphagia following intubation varies widely across the

literature (Ferraris et al., 2001; Tolep et al., 1996) with an overall paucity of studies

INTRODUCTION 56

focusing on post-extubation dysphagia (Ajemian et al., 2001; Atkins et al., 2010; Atkins

et al., 2007; Barker et al., 2009; Barquist et al., 2001; Bordon et al., 2011; Brodsky et al.,

2014; Brown et al., 2011; de Larminat et al., 1995; de Medeiros et al., 2014; DeVita &

Spierer-Rundback, 1990; El Solh et al., 2003; Elpern et al., 1994; Ferraris et al., 2001;

Hafner et al., 2008; Harrington et al., 1998; Keeling et al., 2007; Kwok et al., 2013;

Leder, Cohn, et al., 1998; Macht, King, et al., 2013; Macht et al., 2011; Messina et al.,

1991; Murty & Smith, 1989; Padovani et al., 2008; Rousou et al., 2000; Tolep et al.,

1996). While it is generally accepted that artificial airways interfere with the ability to

execute a safe swallow, the evidence surrounding the relation between intubation

duration and swallow function is still undetermined across patients with varying

diagnoses. Discrepancies exist in the literature regarding both incidence and risk factors

particularly following CV surgery with little consensus on predictive risk factors for

dysphagia in general. It still remains to be determined how frequently dysphagia occurs

following extubation and how to maximize positive patient outcomes.

The definition of prolonged intubation varies throughout the dysphagia (Ajemian

et al., 2001; Barker et al., 2009; de Larminat et al., 1995; El Solh et al., 2003; Tolep et al.,

1996) and CV surgery literature (Cheng et al., 1996; Christian et al., 2011; Cislaghi et al.,

2009; Cohen et al., 2000; Habib et al., 1996; Légaré et al., 2001; Pappalardo et al., 2004;

Reddy et al., 2007; Trouillet et al., 2009; Widyastuti et al., 2012; Yende & Wunderink,

2002). While prolonged intubation is a risk factor for dysphagia following CV surgery

(Barker et al., 2009; Hogue et al., 1995; Rousou et al., 2000), most studies report

cumulative dysphagia frequencies regardless of intubation period (Ferraris et al., 2001;

Hogue et al., 1995; Rousou et al., 2000). No study to date has reported dysphagia frequency according to specific intubation durations following both coronary artery

INTRODUCTION 57

bypass grafting and valve surgery. In particular, dysphagia frequencies following

intubation durations of less than 24 hours or between 24 to 48 hours have yet to be

determined and as a result, it is still unknown as to which patients are at greatest risk of

the disorder following CV surgery.

The number of studies that focus on dysphagia following CV surgery are few

(Barker et al., 2009; Burgess et al., 1979; Ferraris et al., 2001; Harrington et al., 1998;

Hogue et al., 1995; Messina et al., 1991; Partik et al., 2003; Rousou et al., 2000), with the majority reporting on dysphagia associated risk factors rather than systematically characterizing the swallowing impairment (Barker et al., 2009; Ferraris et al., 2001;

Hogue et al., 1995; Messina et al., 1991; Rousou et al., 2000). Many studies are limited by their dysphagia descriptions (Burgess et al., 1979; Harrington et al., 1998; Hogue et al., 1995), assessment methods (Burgess et al., 1979; Harrington et al., 1998), and inclusion criteria (Partik et al., 2003). At present, no study to date has analyzed swallowing physiology using standardized rating scales or objective physiological measurement and as a result, the mechanisms underlying dysphagia following CV surgery have yet to be determined.

Purposes The overarching goal of this body of research was to determine which patients are at greatest risk of dysphagia following CV surgery and in so doing, elucidate the relation between the duration of endotracheal intubation and dysphagia. We conducted three studies in order to meet this goal, with a focus on the cardiovascular surgical population, while addressing the discrepancies in both the incidence of post-extubation dysphagia as well as its associated risk factors. Our primary objectives were to determine: 1) the incidence of dysphagia following endotracheal intubation across diagnostic groups with a

INTRODUCTION 58

focus on the cardiovascular surgical population, 2) the patient characteristics associated

with dysphagia following CV surgery and 3) the feasibility of determining dysphagia

incidence and swallowing physiology prospectively following CV surgery using a

homogeneous, consecutive patient sample.

Our first study protocol addressed the first two primary objectives. We conducted a systematic review in order to evaluate the literature regarding the incidence of dysphagia following endotracheal intubation along with its associated risk factors across a variety of patient diagnostic groups. In addition, we investigated the relationship of endotracheal intubation duration and dysphagia in the published literature. Our second study protocol also addressed the first two primary objectives, however, this time using a homogeneous cardiovascular surgical patient population and a retrospective design. In this study, we stratified the patients according to intubation duration in order to determine dysphagia frequencies according to each stratum. Across the entire patient sample, we also investigated the risk factors associated with dysphagia following CV surgery.

Together, these objectives satisfied the goal of determining those at greatest risk of dysphagia following CV surgery and provide the foundation for our third study. Our third study objective described the feasibility of: 1) determining the incidence of dysphagia prospectively and 2) describing swallowing physiology of consecutively enrolled patients following CV surgery after prolonged intubation. In this study, we evaluated the impact and tolerability on patients and nurses of conducting instrumental swallowing assessments. The results of this study would ultimately inform a future large-

scale protocol which will systematically determine dysphagia incidence and patient’s

swallowing physiology following prolonged intubation after CV surgery using prospective enrollment.

SYSTEMATIC REVIEW

CHAPTER II

THE INCIDENCE OF DYSPHAGIA FOLLOWING ENDOTRACHEAL INTUBATION: A SYSTEMATIC REVIEW

This chapter has been previously published in the journal Chest (Skoretz,

Flowers, & Martino, 2010). The format and references for this chapter have been revised

to conform to the requirements set forth by the School of Graduate Studies at the

University of Toronto. Permission was obtained from the American College of Chest

Physicians to reproduce this copyrighted material in this format (license numbers:

2891530934800, 2891531334875, 2891561082923, 2891561216033; Appendix A).

Abstract

Hospitalized patients are often at increased risk of oropharyngeal dysphagia

following prolonged endotracheal intubation. While reported incidence can be high, it

varies widely. We conducted a systematic review to determine the: 1) incidence of

dysphagia following endotracheal intubation, 2) association between dysphagia and

intubation time and 3) patient characteristics associated with dysphagia. Fourteen electronic databases were searched, using keywords dysphagia, deglutition disorders and intubation, along with manual searching of journals and grey literature. Two reviewers, blinded to each other, selected and reviewed articles at all stages according to our inclusion criteria: adult participants who underwent intubation and clinical assessment for dysphagia. Exclusion criteria were case series (n<10), dysphagia determined by patient report, patients with tracheostomies, esophageal dysphagia, and/or diagnoses known to cause dysphagia. Critical appraisal utilized the Cochrane Risk of Bias assessment and

GRADE tools. A total of 1,489 citations were identified, of which 288 articles were reviewed and 14 met inclusion criteria. The studies were heterogeneous in design,

SYSTEMATIC REVIEW 60 swallowing assessment and study outcome therefore we present findings descriptively.

Dysphagia frequency ranged from 3% to 62% and intubation duration from 124.8 to

346.6 mean hours. The highest dysphagia frequencies, 62%, 56%, and 51%, occurred following prolonged intubation and included patients across all diagnostic subtypes. All studies were limited by design and risk of bias. Overall quality of the evidence was very low. This review highlights the poor available evidence for dysphagia following intubation and hence the need for high quality prospective trials.

SYSTEMATIC REVIEW 61

Introduction

Endotracheal intubation and ventilatory support are life-sustaining procedures often required during the course of a patient’s hospitalization, but their presence can complicate resumption of oral intake (DeVita & Spierer-Rundback, 1990; Tolep et al.,

1996). Artificial airways often have negative effects on laryngeal competence and overall swallowing physiology (DeVita & Spierer-Rundback, 1990; Tolep et al., 1996). It remains to be determined whether oropharyngeal dysphagia, if present, is attributed to the artificial airway alone or in part to the underlying medical conditions that precipitated its placement. Notwithstanding this uncertainty, patients on prolonged ventilation comprise a diagnostic group at increased risk of oropharyngeal dysphagia (Ajemian et al., 2001;

DeVita & Spierer-Rundback, 1990; El Solh et al., 2003; Tolep et al., 1996).

Oropharyngeal dysphagia, also referred to as dysphagia or disordered swallowing, is an abnormality of the swallow physiology of the upper aerodigestive tract. It occurs frequently in patients with structural or neurological disruption to the head and neck area from diseases such as stroke (Martino et al., 2005), head and neck cancer (Ward et al.,

2002) and/or necessary medical treatments including cervical spine surgery (Smith-

Hammond et al., 2004), prolonged intubation (Ajemian et al., 2001; El Solh et al., 2003), tracheotomy (Bonanno, 1971; DeVita & Spierer-Rundback, 1990) and mechanical

ventilation (DeVita & Spierer-Rundback, 1990; Elpern et al., 1994; Tolep et al., 1996).

While dysphagia is itself not a disease but rather a symptom of another medical condition

and/or the interventions required to treat the condition, it can lead to a variety of medical

complications. Common consequences of dysphagia include dehydration, malnutrition

(Smithard et al., 1996; Westergren et al., 2001), aspiration of oral secretions (Murray et

al., 1996), food or fluid (Lundy et al., 1999; Smith, Logemann, Colangelo, Rademaker, &

SYSTEMATIC REVIEW 62

Pauloski, 1999) and eventually death (Smithard et al., 1996). Aspiration often leads to

pneumonia (Holas, DePippo, & Reding, 1994; Johnson, McKenzie, & Sievers, 1993;

Loeb et al., 1999; Lundy et al., 1999; Martino et al., 2005). In fact, the risk of developing

pneumonia is 11 times greater in patients who aspirate compared to similar patients with

no aspiration (Martino et al., 2005).

Although the literature reports a high incidence of dysphagia following

intubation, these reports vary widely from 3% (Ferraris et al., 2001) to 83% (Tolep et al.,

1996). Studies have also shown that prolonged intubation can be an independent

predictor of dysphagia (Barker et al., 2009; Hogue et al., 1995). Artificial airways

increase the risk of upper airway injury and concomitant laryngeal pathologies (Sellery et

al., 1978; Stauffer et al., 1981; Sue & Susanto, 2003), which in turn affect upper airway mechanics, aerodynamics and protective reflexes (DeVita & Spierer-Rundback, 1990;

Tolep et al., 1996). These laryngeal pathologies include, but are not limited to, epithelial/mucosal abrasions, tracheo-esophageal fistula formation, tracheal stenosis and granulation tissue (Stauffer et al., 1981; Sue & Susanto, 2003). Multiple ventilation cycles can further exacerbate the dysphagia by disrupting the delicate synchrony between swallowing and breathing, leading to aspiration (Elpern et al., 1994). While the cause of dysphagia in these patients is multifactorial and perhaps debatable (Leder & Ross, 2000;

Terk, Leder, & Burrell, 2007), it is clear from the available literature that artificial airways interfere with the ability to execute an efficient and safe swallow. What is not yet known is how frequently dysphagia occurs and how to avoid its ill effects.

In order to evaluate the available evidence and attempt to resolve these uncertainties, we conducted a systematic review to assess a) the incidence of dysphagia following intubation across various patient diagnostic groups, b) the association between

SYSTEMATIC REVIEW 63

dysphagia and the duration of endotracheal intubation and c) patient characteristics

associated with dysphagia.

Materials and Methods

A detailed protocol directed the various stages of our search and appraisal of the

literature on dysphagia and endotracheal intubation (see Appendix A).

Operational Definitions

We operationalized relevant terms a priori. Endotracheal intubation was defined

as the presence of an endotracheal tube in the oropharynx. Oropharyngeal dysphagia was

defined as any impairment or abnormality of the oral, pharyngeal or upper esophageal

stage of deglutition. The presence of oropharyngeal dysphagia was identified by either a

clinical bedside swallow evaluation (CSE) or instrumental assessment, including

videofluoroscopic swallow study (VFS) or fiberoptic endoscopic evaluation of the

swallow (FEES).

Search Strategy

From the start of online availability to May 2009, we searched for eligible

citations in 14 electronic databases (MEDLINE [1950-] EMBASE [1980-], CINAHL

[1982-], PsycINFO [1960-], AMED [1985-], HealthSTAR [1966-], BIOSIS Previews

[1980-], Cochrane DSR [1988-], ACP Journal Club [1991-], DARE [1991-], CCTR

[1991-], CMR [1995-], HTA [2001-], and NHSEED [1995-]) using the search terms

deglutition disorders, swallowing disorders, dysphagia, swallowing and intubation. In addition, we manually searched for relevant citations in twenty content related journals between 1988 and May 2009, conference proceedings, and grey/unpublished literature

(GrayLIT Network, GreySource, OpenSigle, and ProQuest Dissertations). We also

SYSTEMATIC REVIEW 64

reviewed citations from the accepted articles. A complete list of manually searched

journals and conference proceedings is available.

Eligibility Criteria

Of the identified citations, we included only articles with abstracts and those

reporting the presence or absence of oropharyngeal dysphagia in adult patients (>18 years

old) who underwent endotracheal intubation during their hospitalization. We accepted

retrospective or prospective study designs using only consecutive enrollment, provided

that the sample size exceeded ten. We included articles published in any language.

Specific to this study, we defined swallowing assessment method to be clinical or

instrumental assessment. In order to avoid overestimating dysphagia incidence secondary

to endotracheal intubation, we excluded articles with patients at high risk for dysphagia

secondary to their primary diagnosis. These included patients with neurogenic or head

and neck diagnoses as well as tracheostomized patients. Articles using only patient report

to identify dysphagia were also excluded.

Study Selection

The first two authors, blinded to each other’s results, reviewed all citations,

abstracts and articles to determine eligibility for inclusion using a form designed a priori

(Appendix B). If the reviewers could not determine inclusion/exclusion based on the abstract alone, the citation was accepted. Articles of all accepted citations were retrieved and reviewed to determine the final studies for inclusion. Disagreements at all stages of

the selection process were resolved by consensus.

Assessment of Methodological Quality

The same two reviewers, once again blinded to each other’s results, assessed the included studies for risk of bias and quality using the Risk of Bias Assessment tool

SYSTEMATIC REVIEW 65

(Appendix C) and the GRADE approach (Grading of Recommendations, Assessment,

Development and Evaluation) as recommended by the Cochrane Collaboration (Higgins,

Green, & Cochrane Collaboration., 2008). All disagreements were resolved by

consensus.

The Risk of Bias Assessment tool (Higgins et al., 2008) included sequence

generation, allocation concealment, blinding, consecutive enrollment, and the

completeness of outcome reporting. Study quality using the GRADE approach gave the

highest rating (high level evidence) to randomized trials while observational studies were

rated as low in quality as suggested by the Cochrane Collaboration (Higgins et al., 2008).

Anticipating a large number of observational studies, we modified this Cochrane quality

rating by downgrading in the presence of certain factors including limitations in study

design, indirectness of evidence (e.g., indirect population or study’s main outcomes),

unexplained heterogeneity, or the imprecision of results. Conversely, study quality was

upgraded if study design and results suggested little to no evidence of bias.

Data Extraction

One reviewer, using a form determined a priori, extracted data regarding study

design, sample size, patient diagnoses, incidence of dysphagia, method of dysphagia

assessment, intubation duration, and patient co-morbidities (Appendix D). A second

reviewer checked all extracted data for accuracy. Due to the heterogeneity of patient diagnoses, study methodology and outcomes across accepted studies; we summarized

results descriptively (see Appendix E for exploratory meta-analyses). Risk of bias

analyses were conducted using the Cochrane Collaboration software program Review

Manager (RevMan, version 5.0.20; The Nordic Cochrane Centre; Copenhagen,

SYSTEMATIC REVIEW 66

Denmark). Quality assessment ratings were adapted from GRADEprofiler©

(GRADEpro©, version 3.2.2; available from http://www.gradeworkinggroup.org).

Results

Literature Retrieved

We retrieved a total of 1,489 citations through database (Appendix F) and manual searching (Figure 2.1). Of these, 351 did not have abstracts and were eliminated. We

reviewed the remaining 1,138 titles and abstracts. An additional 848 abstracts were

eliminated because they: were case series with sample sizes of less than 10, did not enroll

patients consecutively, included pediatric patients, did not report swallowing outcomes,

and included patients following tracheotomy. Two articles were not retrievable (Sarroca

et al., 2003; Vasilev, Germanova, Tzaner, Shwabe, & Karadimov, 2005). We retrieved

and reviewed the full text articles of the remaining 288 citations. Of these, 14 languages

were represented including English (Appendix G). Following full article review, 274

articles were eliminated because they did not meet our inclusion criteria. Of those, 58

articles used only patient report of dysphagic symptoms, 31 articles included patients

with esophageal diagnoses, 27 articles included patients with primary diagnoses of head

and neck cancer and/or neurogenic diagnoses (e.g., stroke, traumatic brain injury, and

neurosurgical patients) and 8 articles did not describe their method for assessing the

swallow. Other article eliminations included: 3 duplicate publications (de Larminat,

Dureuil, Montravers, & Desmonts, 1992; de Larminat, Montravers, Dureuil, &

Desmonts, 1991; Laryea & Ajemian, 2006) using patients from studies accepted for this

review (Ajemian et al., 2001; de Larminat et al., 1995), 2 articles (Leder, Sasaki, &

Burrell, 1998; Leder & Suiter, 2008) with study samples based on only patients referred for suspected dysphagia and 1 article (Partik et al., 2000) that enrolled only patients with

SYSTEMATIC REVIEW 67 confirmed dysphagia. A total of 50 citations, 45 articles and 5 abstracts, were retrieved from manual searches (Appendix H). Six studies were accepted following manual searching: 3 articles (Barker et al., 2009; Ferraris et al., 2001; Keeling et al., 2007) from content related journals, 2 articles (Burgess et al., 1979; Stanley et al., 1995) from the bibliographic references of accepted studies and 1 article (Padovani et al., 2008) from review of grey literature databases. In the end, a total of 14 articles were accepted and underwent further analysis (Table 2.1). A comprehensive list of articles not accepted for full review is available from the authors on request.

SYSTEMATIC REVIEW 68

1,489 citations recovered by database and manual searches

351 eliminated (citations without abstracts)

1,138 titles and abstracts reviewed

848 eliminated (abstracts not meeting inclusion criteria)

2 eliminated (articles not retrievable) 288 full text articles retrieved and reviewed

144 eliminated (articles not meeting inclusion criteria)

58 eliminated (patient report of dysphagia symptoms)

31 eliminated (esophageal diagnoses)

27 eliminated (head/neck cancer and neurogenic diagnoses)

8 eliminated (dysphagia assessment method not described)

3 eliminated (confirmed or suspected dysphagia)

3 eliminated (duplicate publications)

14 articles accepted for review

Figure 2.1. Study selection process.

SYSTEMATIC REVIEW 69

Study Characteristics and Quality Assessment

Of the 14 accepted articles (Table 2.1), 11 were prospective including 2 randomized trials (Barquist et al., 2001; Stanley et al., 1995), 3 cohort studies (Burgess et al., 1979; Davis & Cullen, 1974; El Solh et al., 2003), 1 case-control study (de Larminat et al., 1995) and 5 case-series (Ajemian et al., 2001; Ferraris et al., 2001; Hogue et al.,

1995; Keeling et al., 2007; Leder, Cohn, et al., 1998). Of the retrospective studies: 2 articles (Barker et al., 2009; Rousou et al., 2000) were case-series and 1 article (Padovani et al., 2008) was a cohort design. Patient diagnoses varied across studies. A total of eight studies (Barker et al., 2009; Burgess et al., 1979; Davis & Cullen, 1974; Ferraris et al.,

2001; Hogue et al., 1995; Keeling et al., 2007; Rousou et al., 2000; Stanley et al., 1995) enrolled surgical patients, and of these, 5 articles (Barker et al., 2009; Burgess et al.,

1979; Ferraris et al., 2001; Hogue et al., 1995; Rousou et al., 2000) enrolled cardiovascular surgery patients and the remaining 3 articles (Davis & Cullen, 1974;

Keeling et al., 2007; Stanley et al., 1995) enrolled patients with mixed surgical diagnoses.

Three other studies (de Larminat et al., 1995; El Solh et al., 2003; Padovani et al., 2008) enrolled patients with mixed medical diagnoses. An additional 3 studies (Ajemian et al.,

2001; Barquist et al., 2001; Leder, Cohn, et al., 1998) enrolled patients with a variety of both medical and surgical diagnoses.

SYSTEMATIC REVIEW 70

Table 2.1

Study characteristics and frequency of dysphagia according to patient diagnosis

Timing of Dysphagia Study Study Design Na Swallowing Assessment Method Assessment Post- Frequency extubation Surgical – cardiovascular only Barker et al (2009) Case-series 254 Screening, CSE and/or VFS NR 130/254 (51%) b c Burgess et al (1979) Cohort 64 Chest x-ray Immediately to 8h 13/64 (20%) d Ferraris et al (2001) Case-series 1,042 Screening, VFS NR 31/1042 (3%) d Hogue et al (1995) Case-series 844 Screening, Barium cineradiography NR 28/844 (3%) d Rousou et al (2000) Case-series 838 Screening, Barium cineradiography NR 23/838 (3%) Surgical - mixede Davis & Cullen (1974) Cohort 26 Chest x-rayb 10 and 15 min 9/26 (35%)c c Keeling et al (2007) Case-series 133 CSE, VFS Within 48h 19/133 (14%) b c Stanley et al (1995) Randomized 40 Chest x-ray NR 1/40 (3%) Mixed - medicalf g deLarminat et al (1995) Case-control 34 Swallow latency measurements Immediately 21/3 (62%) c El Solh et al (2003) Cohort 84 FEES Within 48h 37/84 (44%) Padovani et al (2008) Cohort 23 CSE 1-5 days 8/23 (35%) Mixed – medical and surgicalh c Ajemian et al (2001) Case-series 48 FEES Within 48h 27/48 (56%) i j c Barquist et al (2001) Randomized 70 CSE and FEES 48±2h , 24±2h 7/70 (10%) c Leder et al (1998) Case-series 20 FEES 24±2h 9/20 (45%)

Note. CSE = clinical swallowing evaluation; VFS = videofluoroscopic swallowing study; FEES = Fiberoptic endoscopic evaluation of the swallow; NR = not reported. a Includes only patients meeting inclusion criteria for this review. b With administration of oral contrast agent. c Dysphagia defined as aspiration only. d Instrumental assessment conducted with only those patients failing dysphagia screening. e Includes limb arthroplasty, thorocotomy or pulmonary resection, abdominal or vascular surgery. f Includes patients with respiratory illnesses, sepsis, liver failure and/or other medical illness. g Dysphagia defined as swallowing latency on day 0. h Includes surgical/medical intensive care patients, critically ill trauma, burns, and/or elective surgical patients. i CSE only. j FEES only.

SYSTEMATIC REVIEW 71

According to Cochrane methodology (Higgins et al., 2008), we assessed each study for

risk of bias and poor study design to generate a quality GRADE (Table 2.2). Of the 14 included studies, one study (Leder, Cohn, et al., 1998) had the lowest risk of bias with only one area

receiving a rating of unclear. Of the two randomized trials, 1 study (Barquist et al., 2001) had

adequate sequence generation and allocation concealment. Only one other study (Stanley et al.,

1995) declared blinding. All 14 studies accounted for their outcomes but only 8 specifically

declared consecutive enrollment (Ajemian et al., 2001; Barker et al., 2009; El Solh et al., 2003;

Ferraris et al., 2001; Hogue et al., 1995; Keeling et al., 2007; Leder, Cohn, et al., 1998; Rousou

et al., 2000). Outcomes were operationally defined in 4 studies (Barker et al., 2009; Barquist et

al., 2001; El Solh et al., 2003; Leder, Cohn, et al., 1998) while only 8 studies (Ajemian et al.,

2001; Burgess et al., 1979; Davis & Cullen, 1974; de Larminat et al., 1995; El Solh et al., 2003;

Leder, Cohn, et al., 1998; Padovani et al., 2008; Stanley et al., 1995) conducted the same

swallow assessment for all study enrollees. All studies received a high or unclear risk of bias

rating in at least one area. Additionally, each study had factors that decreased the quality of the

evidence such as i) insensitive swallowing assessment measures (Burgess et al., 1979; Davis &

Cullen, 1974; de Larminat et al., 1995; Stanley et al., 1995), ii) small sample size of less than 50

enrollees (Ajemian et al., 2001; Davis & Cullen, 1974; de Larminat et al., 1995; Leder, Cohn, et

al., 1998; Padovani et al., 2008; Stanley et al., 1995) and iii) different types of swallowing

assessment for enrollees (Barker et al., 2009; Ferraris et al., 2001; Hogue et al., 1995; Keeling et

al., 2007; Rousou et al., 2000). As a result, each study in this review was assigned a GRADE of

very low.

SYSTEMATIC REVIEW 72 Table 2.2

Risk of bias and methodological quality (GRADE) across studies

Consistent All Outcomes Sequence Allocation Consecutive Assessment Study Blinding Outcomes Operationally GRADE Generation Concealment Enrollment for All Addressed Defined Enrollees Ajemian et al N/A N/A Unclear Yes Yes Unclear Yes Very Low (2001) Barker et al (2009) N/A N/A Unclear Yes Yes Yes No Very Low Barquist et al Yes Yes No N/A Yes Yes N/A Very Low (2001) Burgess et al Unclear Unclear Unclear Unclear Yes No Yes Very Low (1979) Davis & Cullen N/A N/A Unclear Unclear Yes No Yes Very Low (1974) deLarminat et al N/A N/A Unclear Unclear Yes No Yes Very Low (1995) El Solh et al (2003) N/A N/A No Yes Yes Yes Yes Very Low

Ferraris et al (2001) N/A N/A Unclear Yes Yes No Unclear Very Low

Hogue et al (1995) N/A N/A No Yes Yes No Unclear Very Low Keeling et al N/A N/A Unclear Yes Yes No No Very Low (2007) Leder et al (1998) N/A N/A Unclear Yes Yes Yes Yes Very Low Padovani et al N/A N/A Unclear Unclear Yes No Yes Very Low (2008) Rousou et al (2000) N/A N/A Unclear Yes Yes No Unclear Very Low

Stanley et al (1995) Unclear Unclear Yes Unclear Yes No Yes Very Low

Note. GRADE = Grading of Recommendations, Assessment, Development and Evaluation; N/A = not applicable.

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Dysphagia Following Endotracheal Intubation

Duration of intubation and the frequency dysphagia. Seven of the included studies

(Ajemian et al., 2001; Barker et al., 2009; Barquist et al., 2001; El Solh et al., 2003; Hogue et al.,

1995; Leder, Cohn, et al., 1998; Rousou et al., 2000) reported mean durations of intubation in those with and without dysphagia (Table 2.3). Leder and his colleagues (1998) reported the lengthiest intubation duration in the dysphagic patients (mean, 346.6 h ± 298.6) with a dysphagia frequency of 45%. Ajemian and his colleagues (2001) reported the highest dysphagia frequency with a mean intubation duration of 192.0h in patients with dysphagia. One study (Barquist et al.,

2001) reported longer intubation durations in patients without dysphagia (mean, 288.0h ± 235.2) compared to those with dysphagia (mean, 254.4h ± 175.2). Five of these studies (Ajemian et al.,

2001; Barker et al., 2009; Barquist et al., 2001; El Solh et al., 2003; Leder, Cohn, et al., 1998) included only enrollees with prolonged intubation defined as greater than 48h.

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Table 2.3

Intubation duration according to presence of dysphagia

Intubation Duration Targeted (h, mean ± SDa) Intubation Dysphagia Study Time Frequency (h) Dysphagia No Dysphagia

Leder et al (1998) >48 346.6 ± 298.6 283.7 ± 192.0 45%

Barquist et al (2001) >48 254.4 ± 175.2 288.0 ± 235.2 10%

Rousou et al (2000) NR 200.9 ± 75.0 15.3 ± 1.6 3%

b El Solh et al (2003) >48 223.2 ± 156.0 184.8 ± 112.8 36%

Ajemian et al (2001) >48 192.0 184.8 56%

c El Solh et al (2003) >48 187.2 ± 165.6 148.8 ± 127.2 52%

Barker et al (2009) >48 142.4 ± 63.0 87.1 ± 43.3 51%

Hogue et al (1995 NR 124.8 ± 40.8 50.4 ± 4.8 3%

Note. h = hour; SD = standard deviation; NR = not reported. a Where reported. b Young age cohort (<65 years old). c Elderly age cohort (>65 years old).

Swallowing assessment methods. The methods used to assess swallowing function were variable. All studies but one (Padovani et al., 2008) used instrumental methods to determine the presence or absence of dysphagia and/or aspiration. Seven studies (Ajemian et al., 2001; Burgess et al., 1979; Davis & Cullen, 1974; de Larminat et al., 1995; El Solh et al., 2003; Leder, Cohn, et al., 1998; Stanley et al., 1995) conducted instrumentation on all study enrollees. Three studies

(Ajemian et al., 2001; El Solh et al., 2003; Leder, Cohn, et al., 1998) used fiberoptic endoscopic evaluation of swallowing (FEES), three studies (Burgess et al., 1979; Davis & Cullen, 1974;

Stanley et al., 1995) used chest radiography following administration of an oral contrast agent, and one study (de Larminat et al., 1995) measured swallowing latency via submental

SYSTEMATIC REVIEW 75

electromyography. Three studies (Ferraris et al., 2001; Hogue et al., 1995; Rousou et al., 2000)

used videofluoroscopic swallowing studies (VFS) or barium cineradiography only on those

patients who failed swallowing screening. Clinical swallowing evaluation (CSE) was the sole

method to assess dysphagia in one study (Padovani et al., 2008) while another study (Barquist et

al., 2001) utilized either CSE and FEES depending on the arm of their randomized trial.

Across studies, swallowing assessments were conducted at various time periods following extubation. Five studies (Ajemian et al., 2001; Barquist et al., 2001; El Solh et al.,

2003; Keeling et al., 2007; Leder, Cohn, et al., 1998) conducted their swallowing assessment between 24 and 48 hours following extubation. Studies using chest radiographs (Burgess et al.,

1979; Davis & Cullen, 1974; Stanley et al., 1995) administered oral contrast at various time points with radiographs taken at two minutes (Stanley et al., 1995), 30 minutes (Burgess et al.,

1979) and 1 hour (Davis & Cullen, 1974) following the contrast ingestion. The study using

electromyography (de Larminat et al., 1995) measured swallow latency immediately (day 0), and

at 1, 2, and 7 days following extubation. One study (Padovani et al., 2008) assessed swallowing

between days 1 and 5 following extubation. For another five studies (Barker et al., 2009; Ferraris

et al., 2001; Hogue et al., 1995; Rousou et al., 2000; Stanley et al., 1995) the timing of

swallowing assessment was not reported.

Frequency of dysphagia following intubation. The incidence of dysphagia across

studies included in this review ranged widely from 3% (Ferraris et al., 2001; Hogue et al., 1995;

Rousou et al., 2000; Stanley et al., 1995) to 62% (de Larminat et al., 1995). Those studies

reporting the highest dysphagia frequencies (Ajemian et al., 2001; Barker et al., 2009; de

Larminat et al., 1995; El Solh et al., 2003; Leder, Cohn, et al., 1998), between 44% and 62%, had

prolonged intubation periods. Three studies (Ferraris et al., 2001; Hogue et al., 1995; Rousou et

SYSTEMATIC REVIEW 76

al., 2000) reporting the lowest dysphagia frequency did not report findings from screening and/or

CSE and only reported dysphagia in those patients with abnormal VFS or barium

cineradiography. One study (Barker et al., 2009) utilized either CSE or VFS to determine dysphagia frequency but did not stratify according to assessment method.

Swallowing impairment as an outcome was defined differently across studies, either as any level of dysphagia severity (Barker et al., 2009; Ferraris et al., 2001; Hogue et al., 1995;

Padovani et al., 2008; Rousou et al., 2000), only aspiration (Ajemian et al., 2001; Barquist et al.,

2001; Burgess et al., 1979; Davis & Cullen, 1974; El Solh et al., 2003; Keeling et al., 2007;

Leder, Cohn, et al., 1998; Stanley et al., 1995) or only swallowing latency (de Larminat et al.,

1995). Regardless of definition, the dysphagia frequencies varied widely. Studies reporting on

any level of dysphagia severity (Barker et al., 2009; Ferraris et al., 2001; Hogue et al., 1995;

Padovani et al., 2008; Rousou et al., 2000) had frequencies ranging from 3% (Ferraris et al.,

2001; Hogue et al., 1995; Rousou et al., 2000) to 51% (Barker et al., 2009). Those studies

reporting only aspiration also had wide ranging frequencies from 3% (Stanley et al., 1995) to

56% (Ajemian et al., 2001).

Several of the included studies identified patient risk factors, surgical and/or medical,

associated with dysphagia (Table 2.4). Some risks were consistently associated with dysphagia

while others were consistently not associated (Table 2.4a). In contrast, some studies reported

association with several risk factors, while others reported no association for the same risk

factors (Table 2.4b).

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Table 2.4a.

Surgical and medical risk factor association with dysphagia

Associated with dysphagia Not associated with dysphagia

APACHE scoresc,f a, b, d, g a,b COPD Congestive heart failure Circulatory shocka, b Functional statusc a,d,e a-e Elevated CPB time Increased hospital LOS GERDg Hypercholesterolemiaa a,b,d c,d Hypertension Increased ICU LOS ICU readmissionb Multiple intubationsb b,d e Myocardial infarction Increased operative time NYHA >2 a,b Peri-operative TEEd,e a b Peripheral vascular disease Sepsis Pre-operative CVAa,b,d Smokingb Surgery urgencyb

Note. APACHE = Acute Physiology and Chronic Health Evaluation; COPD = chronic obstructive pulmonary disease; CPB = cardiopulmonary bypass; GERD = gastro-esophageal reflux disease; LOS = length of stay; ICU = intensive care unit; NYHA = New York Heart Association staging (heart failure); TEE = trans-esophageal echocardiography; vascular accident; CVA = cerebral. a Ferraris et al., 2001. b Barker et al., 2009. c El Solh et al., 2003. d Hogue et al., 1995. e Rousou et al., 2000. f deLarminat et al., 1995. g Ajemian et al., 2001.

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Table 2.4b

Studies either supporting or not supporting risks for dysphagia

Association with Dysphagia Risk Factors Supporting Not Supporting

Ajemian et al (2001) Barquist et al (2001) deLarminat et al (1995) Age Ferraris et al (2001) Leder et al (1998) Hogue et al (1995) Rousou et al (2000)

Decreased cardiac output Hogue et al (1995) Barker et al (2009)

Ajemian et al (2001) Diabetes mellitus Ferraris et al (2001) Barker et al (2009) Hogue et al (1995) Ajemian et al (2001) Barker et al (2009) Barquist et al (2001) Intubation duration Hogue et al (1995) deLarminat et al (1995) Rousou et al (2000) El Solh et al (2003) Leder et al (1998)

Left ventricle ejection fraction Rousou et al (2000) Hogue et al (1995)

Barker et al (2009) Peri-operative CVA Rousou et al (2000) Hogue et al (1995) Post-operative pulmonary Hogue et al (1995) Leder et al (1998) complications

a Pre-op/post-op IABP Hogue et al (1995) Barker et al (2009)

Barker et al (2009) Renal risks Ferraris et al (2001) Hogue et al (1995)

b Barker et al (2009) Hogue et al (1995) Surgery type c Ferraris et al (2001) Rousou et al (2000)

Ajemian et al (2001) Tube feeding Barker et al (2009) El Solh et al (2003) Leder et al (1998)

Note. CVA = cerebral vascular accident; IABP = intra-aortic balloon pump. a Post-operative IABP only. b Coronary artery bypass. c Non-coronary procedures.

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Discussion

This systematic review verifies that reported dysphagia frequency following endotracheal

intubation is variable, ranging from 3% (Ferraris et al., 2001; Hogue et al., 1995; Rousou et al.,

2000; Stanley et al., 1995) to 62% (de Larminat et al., 1995). Over half of the studies (Ajemian et al., 2001; Barker et al., 2009; Burgess et al., 1979; Davis & Cullen, 1974; de Larminat et al.,

1995; El Solh et al., 2003; Leder, Cohn, et al., 1998; Padovani et al., 2008) reported a dysphagia frequency exceeding 20%. The highest dysphagia frequencies of 62% (de Larminat et al., 1995),

56% (Ajemian et al., 2001) and 51% (Barker et al., 2009) included patients experiencing

prolonged intubation (>24 hours) across all diagnostic subtypes, mixed medical, mixed medical-

surgical and cardiovascular surgical groups respectively. Hence, no single diagnosis appeared to

be associated with greater risk of dysphagia. The wide range of dysphagia frequency identified in

this review is more likely attributed to variations in study design, such as method and timing of

swallowing assessment. Many studies were observational and few declared blinding or operational definitions. Together, design variability and poor quality resulted in studies with a high risk of bias; thereby weakening the available evidence on dysphagia frequency following endotracheal intubation.

Across all studies, poor study quality and high risk of bias likely led to either under or over reporting of dysphagia. Oddly, studies reporting the longest intubation duration did not report the highest dysphagia frequencies (Barquist et al., 2001; Leder, Cohn, et al., 1998; Rousou et al., 2000). However, their large standard deviations (Barquist et al., 2001; Leder, Cohn, et al.,

1998), coupled with failure to use the same instrumental assessments for all enrollees (Rousou et al., 2000), seriously questions the accuracy of these frequency estimates. In contrast, three studies reporting the lowest dysphagia frequencies had the largest sample sizes (Ferraris et al.,

SYSTEMATIC REVIEW 80

2001; Hogue et al., 1995; Rousou et al., 2000). We also question the accuracy of these frequency

estimates as they appeared to include patients with relatively short intubation durations and

consequently not expected to have dysphagia. Across studies, the timing of swallowing

assessments ranged from immediately (Burgess et al., 1979; de Larminat et al., 1995) to five

days (Padovani et al., 2008) following extubation. In general, one would expect the highest

dysphagia frequency in patients with prolonged intubation durations and assessments conducted

immediately following extubation. However, due to the poor study quality and variability of the

included studies our findings could not corroborate this premise.

A wide assortment of swallowing assessment methods, including screening, clinical swallowing evaluations and a variety of instrumental assessments, were included in the accepted studies. Dysphagia frequency varied regardless of assessment type. Although heterogeneity across studies did not permit a statistical association of dysphagia frequency and swallow assessment, studies using FEES on all enrollees reported some of the highest frequencies of dysphagia from 44% (El Solh et al., 2003) to 56% (Ajemian et al., 2001). In contrast, other

studies assessing the swallow with static chest radiographs (Burgess et al., 1979; Davis &

Cullen, 1974; Stanley et al., 1995) or clinical measures (Padovani et al., 2008) detected a lower

incidence of dysphagia, from 3% (Stanley et al., 1995) to 35% (Davis & Cullen, 1974; Padovani

et al., 2008). When compared with other swallowing assessment methods, direct visualization of

pharyngeal and laryngeal swallowing structures (e.g. FEES) may be a more sensitive measure

(Kelly et al., 2007; Kelly et al., 2006).

Studies varied in how swallowing outcomes were defined. Over half of the included

studies (Ajemian et al., 2001; Barquist et al., 2001; Burgess et al., 1979; Davis & Cullen, 1974;

El Solh et al., 2003; Keeling et al., 2007; Leder, Cohn, et al., 1998; Stanley et al., 1995) used

SYSTEMATIC REVIEW 81

aspiration as their main swallowing outcome. Aspiration is only one aspect across the spectrum

of swallowing impairments. While aspiration is considered dysphagia in its most severe form,

defining dysphagia as such would limit diagnostic scope and potentially miss other significant

swallowing findings. For example, one study (Barquist et al., 2001) reporting a low incidence of

dysphagia (10%) also commented on other pharyngeal aspects of the swallow. These findings

were reported only qualitatively thereby explaining, in part, their low reported frequency.

Although we used stringent selection criteria and rigorous methodology while excluding

confounding diagnoses for dysphagia, this review is limited by many factors. Most limitations

were imposed by the design, quantity and quality of the original research. The few included

studies were heterogeneous, differing in regard to their outcomes, study design and patient

diagnoses. Consequently, instead of combining outcome data with a meta-analysis, we chose to employ descriptive methods. We found insufficient evidence to: 1) calculate the relative risk of dysphagia following a range of intubation durations and 2) to determine effect of intubation duration on the frequency of dysphagia across all studies. We propose that using sensitive swallow assessments on all enrollees, while reporting on all aspects of swallowing function, would best represent the frequency and characteristics of dysphagia following extubation.

Future research endeavours should include homogeneous patient populations or larger sample sizes and rigorous methodology. This research is necessary to permit clinicians to identify patients who are at greater risk of dysphagia and enable more appropriate interventions.

In conclusion, there are relatively few studies with specific outcomes focusing on dysphagia following intubation. The majority of identified studies are of very low quality with high risk of bias. Although variable, most studies with prolonged intubation durations and those that conducted instrumental assessments on the entire study population reported higher

SYSTEMATIC REVIEW 82 frequencies of dysphagia. Given the high likelihood of serious medical complications of dysphagia, particularly pneumonia, we recommend that swallowing assessments should be conducted on patients undergoing prolonged intubation durations. In the meantime, we call for high quality studies using homogeneous patient populations to assess the influence of prolonged intubation on dysphagia and to determine whether select medical comorbidities put patients at greater risk.

RETROSPECTIVE STUDY

CHAPTER III

DYSPHAGIA AND ASSOCIATED RISK FACTORS FOLLOWING EXTUBATION IN CARDIOVASCULAR SURGICAL PATIENTS

This chapter has been previously published in the journal, Dysphagia (Skoretz, Yau,

Ivanov, Granton, & Martino, 2014). The format and references for this chapter have been

revised to conform to the requirements set forth by the School of Graduate Studies at the

University of Toronto. Permission was obtained from the publisher, Springer, to reproduce this

copyrighted material in this format (license number: 3493380167372, Appendix J).

Abstract

Following cardiovascular (CV) surgery, prolonged mechanical ventilation >48 h increases dysphagia frequency over tenfold: 51 % in compared to 3-4 % across all durations.

Our primary objective was to identify dysphagia frequency following CV surgery with respect to intubation duration. Our secondary objective was to explore characteristics associated with dysphagia across the entire sample. Using a retrospective design, we stratified all consecutive patients who underwent CV surgery in 2009 at our institution into intubation duration groups defined a priori: I (≤12 h), II (>12 to ≤24 h), III (> 24 to ≤ 48 h), and IV (>48 h). Eligible patients were >18 years old who survived extubation following coronary artery bypass alone or cardiac valve surgery. Patients who underwent tracheotomy were excluded. Two blinded reviewers extracted pre-, peri- and postoperative patient variables from a pre-existing database and medical charts. Disagreements were resolved by consensus. Across the entire sample, multivariable logistic regression analysis determined independent predictors of dysphagia.

Across the entire sample, dysphagia frequency was 5.6 % (51/909) but varied by group: I, 1 %

(7/699); II, 8.2 % (11/134); III, 16.7 % (6/36); and IV, 67.5 % (27/40). Across the entire sample,

RETROSPECTIVE STUDY 84

the independent predictors of dysphagia included intubation duration in 12-h increments

(p < .001; odds ratio [OR] 1.93, 95 % confidence interval [CI] 1.63-2.29) and age in 10-year

increments (p = .004; OR 2.12, 95 % CI 1.27-3.52). Patients had a twofold increase in their odds of developing dysphagia for every additional 12 h with endotracheal intubation and for every additional decade in age. These patients should undergo post-extubation swallow assessments in order to minimize complications.

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Introduction

Dysphagia is a recognized complication following extubation that can lead to increased

morbidity, mortality (Macht et al., 2011), and hospital costs (Ferraris et al., 2001). While a patient’s dysphagia risk increases following prolonged periods of mechanical ventilation, no study to date has reported dysphagia frequencies across stratified intubation durations following both coronary artery bypass grafting and cardiac valve surgery (Skoretz, Flowers, et al., 2010).

All patients undergoing cardiovascular (CV) surgery require endotracheal intubation and

mechanical ventilation as part of standard surgical intervention; however, the duration of

intubation after surgery varies (Cislaghi et al., 2009; Reddy et al., 2007). When intubation duration exceeds 48 h following CV surgery, the frequency of swallowing impairments

(dysphagia) is 51 % (Barker et al., 2009), approximately ten times greater than that of the CV surgical population as a whole (Ferraris et al., 2001; Hogue et al., 1995; Rousou et al., 2000).

The number of studies that focus on dysphagia following CV surgery are few (Barker et

al., 2009; Burgess et al., 1979; Ferraris et al., 2001; Harrington et al., 1998; Hogue et al., 1995;

Messina et al., 1991; Partik et al., 2003; Rousou et al., 2000) and the evidence surrounding the

relation between intubation duration and dysphagia in this population is limited (Skoretz,

Flowers, et al., 2010). In particular, most studies addressing intubation duration report

cumulative dysphagia frequencies regardless of intubation periods (Ferraris et al., 2001; Hogue

et al., 1995; Rousou et al., 2000), with only two (Barker et al., 2009; Burgess et al., 1979)

focusing on specific intubation durations: >48 h (Barker et al., 2009) and from 8 to 28 h (Burgess

et al., 1979). As a result, dysphagia frequencies following intubation durations of <24 h or

between 24 and 48 have yet to be reported. In addition to the limitations in the CV surgery

literature, discrepancies also exist regarding the definition of prolonged intubation in other

RETROSPECTIVE STUDY 86 diagnostic groups (Ajemian et al., 2001; de Larminat et al., 1995; Leder, Cohn, et al., 1998;

Tolep et al., 1996). In those studies prolonged intubation is defined as >24 h (de Larminat et al.,

1995), >48 h (Ajemian et al., 2001; Leder, Cohn, et al., 1998) or as long as 8 days (Tolep et al.,

1996). Overall, dysphagia following extubation regardless of the diagnostic group requires further investigation (Skoretz, Flowers, et al., 2010).

Our primary goal was to report the frequency of dysphagia according to varying intubation duration following coronary artery bypass grafting and/or cardiac valve surgery.

Furthermore, we also sought to explore the characteristics associated with dysphagia across this

CV surgical population thereby determining those at greatest risk for dysphagia.

Patients and Methods

Following institutional ethics board approval, we retrospectively reviewed the medical records of all consecutive patients who underwent CV surgery in a 12-month period (January-

December 2009) at a single institution. We included adult patients (>18 years of age) who survived their final extubation following coronary artery bypass alone or valve replacements and/or repairs as their primary procedure. We excluded patients who underwent cardiac transplantation, implantation of ventricular assist devices, repair of adult congenital heart defects, and other complex procedures. Patients who underwent a pre- or postoperative tracheotomy were also excluded.

Data Abstraction

Demographic, clinical, and operative patient data from electronic medical charts and the existing CV surgery database were utilized for this study.

The electronic chart review was conducted in accordance with a data abstraction manual that we developed and finalized a priori (Appendix K). Two raters (SAS and a research

RETROSPECTIVE STUDY 87

assistant), blinded to each other, reviewed the electronic charts of all patients who met the

study’s inclusion criteria. The reviewers recorded data regarding (1) extubation dates and times,

(2) perioperative transesophageal echocardiography, and (3) medical orders and nursing staff

documentation pertaining to tube feeding, assessment by speech-language pathology (SLP), and

dietary texture modifications. Data were recorded using a pre-established form (Appendix L).

Disagreements between raters were resolved by consensus.

The CV surgery database is completed prospectively for all patients who undergo CV surgery at our institution (Rao et al., 1996). Trained CV surgery research nurses collect and enter the data. Their reliability is regularly monitored through internal chart audits. Only the variables of interest were extracted for this study, including those pertaining to demographics as well as preoperative, perioperative, and postoperative outcomes.

Operational Definitions

Both intubation duration strata and oropharyngeal dysphagia were defined a priori.

Specifically, intubation durations were grouped into four strata: I (≤12 h), II (>12 to ≤24 h), III

(>24 to ≤48 h), and IV (>48 h). Dysphagia was defined as any abnormality of the oral, pharyngeal, or upper esophageal stage of deglutition resulting in impairment in swallowing.

Impairment was identified by any one of the following medical orders that occurred within 96 h following the patient’s final extubation: (1) enteral feeding, (2) swallowing assessment order recommending enteral feeding, modified-texture diet, or nil per os (NPO), or (3) modified texture diet order as written by a speech-language pathologist or medical staff.

Statistical Analyses

We reported data as frequency, mean with standard deviation (SD), and median with interquartile range (IQR) as appropriate. The frequency of dysphagia was summarized

RETROSPECTIVE STUDY 88 descriptively. Comparisons were made between those with and those without dysphagia across the entire study sample, using Mann-Whitney or unpaired 2-sided t-tests for continuous variables and Pearson’s χ2 test or Fisher’s exact test for proportions. Missing variables were imputed with the median. Variables for our main-effect regression model were selected using a backward stepwise bootstrapping method (n = 1,000, inclusion threshold p < .05). In order to avoid colinearity, predictor variables that were deemed clinically redundant were not entered into the bootstrap. We considered variables occurring in >10 % of the bootstrapping resamples for our final model. Our final regression was conducted using a backward stepwise method. For the purposes of the bootstrap and regression, the following variables were dichotomized and/or defined as: (1) moderate left ventricular (LVEF <40 %) dysfunction, (2) New York Heart

Association (NYHA) class IV symptoms, (3) myocardial infarction within 30 days preoperatively, and (4) a nonelective surgical procedure.

Bivariate analyses were conducted using IBM® SPSS© v19.0 for Mac OS X (IBM®,

Armonk, NY, USA). Bootstrap and regression modeling were conducted using SAS v9.1 for

Windows (SAS Institute Inc., Cary, NC, USA). We determined statistical significance by a 2- tailed p < .05.

Results

A total of 1,480 patients underwent CV surgery between January 1 and December 31,

2009, at our institution. Of those, 944 patients underwent coronary artery bypass grafting or valve repairs and/or replacements as their primary procedures. Of the 944 patients, a total of 35 patients were excluded: 17 patients died while intubated, 17 underwent a tracheotomy, and one patient had no recorded intubation time. The remaining 909 patients were then stratified according to intubation duration: I (≤12 h) included 699 patients (76.9 % of total), II (>12 to ≤24

RETROSPECTIVE STUDY 89 h) 134 patients (14.7% of total), III (>24 to ≤48 h) 36 patients (4.0% of total), and IV (>48 h) 40 patients (4.4 % of total). This sample size met a total sample required to meet expected event rate in our intubation groups (see Appendix M for sample size calculation).

Dysphagia Frequency and Criteria

Dysphagia frequency was 5.6% (51/909) across the entire study sample but varied across intubation groups: I, 1.0 % (7/699); II, 8.2 % (11/134); III, 16.7 % (6/36); and IV, 67.5 % (27/40)

(Table 3.1). Of the 51 patients with dysphagia, 47 (92 %) patients met two or more of our criteria for dysphagia, with nearly half (25/51, 49 %) meeting all three. Four patients (8 %) met only one of our dysphagia criteria. All four of these patients required enteral feeding as their primary form of nutrition and had a Glasgow Coma Score (GCS) of 14 or higher. The first dysphagia criterion was met within 24 h following extubation for 19 patients (37 %), within 48 h for 18 patients (35 %), within 72 h for nine patients (18 %) and within 96 h for 5 (10 %) patients.

RETROSPECTIVE STUDY 90

Table 3.1

Comparing dysphagia frequency and intubation duration across intubation groups

Dysphagia frequency

Intubation group Without Total With dysphagia dysphagia (n = 909) (n = 51) (n = 858)

Ia 699 (76.9) 692 (80.7) 7 (13.7)

IIb 134 (14.7) 123 (14.3) 11 (21.6)

IIIc 36 (4.0) 30 (3.5) 6 (11.8)

IVd 40 (4.4) 13 (1.5) 27 (52.9)

Note. Values are n (%); h = hours. a I, ≤ 12.0 h; b II, >12.0 h and ≤24.0 h ; c III, >24.0 h and ≤48.0 h; d IV, >48.0 h.

Intubation Duration Across Study Sample

Median intubation duration [IQR] for all patients was 6.9 h [6.2]. Across the entire

sample, those with dysphagia had significantly longer median intubation duration than those

without (68.8 h [93.7] vs. 6.8 h [5.2]; p < .001).

Patient Characteristics Across Study Sample

Demographic variables and preoperative clinical characteristics are presented in Table

3.2. Across the sample, the mean (±SD) age was 65.9 years (±12.0). Those with postoperative dysphagia were significantly older than those without (74.3 ± 8.7 vs. 65.4 ± 12.0 years; p <

.001), with proportionately more having at least moderate chronic kidney disease (58.8 vs. 19.9

%; p < .001). Cardiovascular surgical risk factors differed between those with and those without

RETROSPECTIVE STUDY 91 dysphagia, including NYHA symptom class (p = .008), congestive heart failure (41.2 vs. 16.9 %, p < .001), preoperative atrial fibrillation (17.6 vs. 5.6 %, p = .003) and preoperative stroke or transient ischemic attack (25.5 vs. 8.7 %, p = .001). Some patient characteristics were not discriminatory, including diabetes, preoperative myocardial infarction, hypertension and respiratory risks such as a history of smoking. Of the entire study sample (n = 909), there was missing data from 1 to 11 patients (0.1-1.2 %) for the following variables: family history of heart disease (1.0 %), diabetes (0.1 %), LV grade (0.4 %), NYHA symptom class (1.2 %), hyperlipidemia (0.2 %), smoking history (0.2 %) and chronic kidney disease (0.1 %) (Table 3.2).

RETROSPECTIVE STUDY 92

Table 3.2

Pre-operative demographics and presenting clinical characteristics across sample

All Without With p- patients dysphagia dysphagia value Variable (n = 909) (n = 858) (n = 51)

Age, mean yrs (SD) 65.9 (12.0) 65.4 (12.0) 74.3 (8.7) < .001

median yrs (IQR) 67.0 (17.0) 67.0 (17.0) 76.0 (12.0) < .001

Male, n (%) 649 (71.4) 612 (71.3) 37 (72.5) .876

Family history of heart diseasea, 476 (52.9) 449 (52.8) 27 (54.0) .885 n (%)

Diabetes Risksb

Diabetesc, n (%) 309 (34.0) 292 (34.0) 17 (33.3) 1.00

Cardiovascular Surgical Risks

Circulatory shock, n (%) 10 (1.1) 9 (1.0) 1 (2.0) .440

Non-Q-wave infarction, n (%) 127 (14.0) 124 (14.5) 3 (5.9) .097

Q-wave infarction, n (%) 15 (1.7) 14 (1.6) 1 (2.0) .582

LV graded .042 1, n (%) 582 (64.3) 556 (65.1) 26 (51.0) 2, n (%) 207 (22.9) 193 (22.6) 14 (27.5) 3, n (%) 107 (11.8) 98 (11.5) 9 (17.6) 4, n (%) 9 (1.0) 7 (0.8) 2 (3.9)

NYHA classificatione .008 I, n (%) 131 (14.6) 130 (15.3) 1 (2.0) II, n (%) 189 (21.0) 183 (21.6) 6 (12.0) III, n (%) 295 (32.9) 273 (32.2) 22 (44.0) IV, n (%) 283 (31.5) 262 (30.9) 21 (42.0)

Congestive heart failure, n (%) 166 (18.3) 145 (16.9) 21 (41.2) <.001

Hypertensive, n (%) 655 (72.1) 616 (71.8) 39 (76.5) .524

RETROSPECTIVE STUDY 93

All Without With p- patients dysphagia dysphagia value Variable (n = 909) (n = 858) (n = 51)

Diet or medically treated 658 (72.5) 620 (72.4) 38 (74.5) .753 hyperlipidemiaf, n (%)

Previous stroke or TIA, n (%) 88 (9.7) 75 (8.7) 13 (25.5) .001

Heart block / pacemaker, n (%) 18 (2.0) 17 (2.0) 1 (2.0) 1.000

Atrial fibrillation or flutter, n (%) 57 (6.3) 48 (5.6) 9 (17.6) .003

Left main artery stenosis, n (%) 209 (23.0) 197 (23.0) 12 (23.5) 1.00

Respiratory Risks

Current or past smokerg, 529 (58.3) 498 (58.0) 31 (63.3) .552 n (%)

Renal Risks

Chronic kidney diseaseh n (%) 201 (22.1) 171 (19.9) 30 (58.8) <.001

Note. yrs = years; LV = left ventricular; NYHA = New York Heart Association; TIA = transient ischemic attack. a Missing data: 8 patients without dysphagia, 1 patient with dysphagia (total: 1.0%). b Missing data: 1 patient without dysphagia (total: 0.1%). c Includes diet controlled, orally medicated and insulin dependent diabetics. d Missing data: 4 patients without dysphagia (total: 0.4%). e Missing data: 10 patients without dysphagia, 1 patient with dysphagia (total: 1.2%). f Missing data: 2 patients without dysphagia (total: 0.2%). g Missing data: 2 patients with dysphagia (total: 0.2%), h At least moderate chronic kidney disease as defined by an estimated creatinine clearance <60mL/min; missing data: 1 patient without dysphagia (total: 0.1%).

RETROSPECTIVE STUDY 94

Of 909 patients, 567 (62.4 %) underwent coronary artery bypass as their primary surgery, with the remaining patients (342/909, 37.6 %) undergoing valve repair and/or replacement. Many operative characteristics and perioperative complications distinguished those with and without dysphagia (Table 3.3). More patients with dysphagia underwent valve repair and/or replacement as compared to coronary artery bypass grafting (60.8 vs. 39.2 %, p = .001) and also required a perioperative transesophageal echocardiogram (74.5 vs. 44.3 %, p < .001). Patients with dysphagia also had more perioperative strokes, sepsis, and low output syndrome. Lastly, more patients with dysphagia required intra-aortic balloon pump placement (15.7 vs. 2.9 %, p < .001) and/or inotropic support (54.9 vs. 39.5 %, p = .039) than patients without.

RETROSPECTIVE STUDY 95

Table 3.3

Peri-operative characteristics across sample

Without With All patients dysphagia dysphagia p-value (n = 909) Variable (n = 858) (n = 51)

Procedure .001 CABG, [n (%)] 567 (62.4) 547 (63.8) 20 (39.2) Valve, [n (%)] 342 (37.6) 311 (36.2) 31 (60.8)

Urgency .701 Elective, [n (%)] 574 (63.1) 543 (63.3) 31 (60.8) Inpatient, [n (%)] 263 (28.9) 245 (28.6) 18 (35.3) Urgent, [n (%)] 59 (6.5) 57 (6.6) 2 (3.9) Emergent, [n (%)] 13 (1.4) 13 (1.5) 0 (0.0)

CPB usage 826 (90.9) 783 (91.3) 43 (84.3) .126

CPB duration, [median 85.0 (41.0) 84.0 (41.0) 94.0 (82.0) .014 (IQR)] (min)

TEE, [n (%)] 418 (46.0) 380 (44.3) 38 (74.5) <.001

Perioperative Complications

Strokea, [n (%)] 10 (1.1) 4 (0.5) 6 (11.8) <.001

Sepsisb, [n (%)] 8 (0.9) 5 (0.6) 3 (5.9) .008

Use of dopamine in ICU, 367 (40.4) 339 (39.5) 28 (54.9) .039 [n (%)]

MI, [n (%)] 13 (1.4) 10 (1.2) 3 (5.9) .032

Low-output syndromec, 20 (2.2) 13 (1.5) 7 (13.7) <.001 [n (%)]

IABP usage 33 (3.6) 25 (2.9) 8 (15.7) <.001

Note. CABG = coronary artery bypass graft; CPB = cardiopulmonary bypass; IQR = interquartile range; min = minutes; ICU = intensive care unit; MI = myocardial infarction; TEE = transesophageal echocardiogram utilized peri- operatively; IABP = intra-aortic balloon pump placement either pre-, peri- or post-operatively. a Evidence of persistent neurological deficit. b Positive blood culture. c Use of inotrope or mechanical devices for more than 30 minutes to maintain a blood pressure > 90mmHg with a C.I.< 2.2 l/m/m2.

RETROSPECTIVE STUDY 96

Postoperative outcomes also differed between those with and without dysphagia

(Table 3.4). In addition to longer intubation durations, those with dysphagia had significantly higher frequencies of reintubation (p = < .001), reoperation (p = < .001) and postoperative atrial fibrillation (p = .002). While patients with dysphagia had longer stays in the intensive care unit (p = < .001), they were not readmitted to the intensive care unit at a greater rate (p = .108). For descriptive data of intubation strata I, II, III, and IV refer to Appendices N, O, P and Q respectively.

RETROSPECTIVE STUDY 97

Table 3.4

Post-operative patient outcomes across sample

Without With All patients Dysphagia Dysphagia p-value (n = 909) Variable (n = 858) (n = 51)

Intubation duration, [median (IQR)] (hours) 6.9 (6.2) 6.8 (5.2) 68.8 (93.7) <.001

Reintubation, [n (%)] 25 (2.8) 13 (1.5) 12 (23.5) <.001

Number of intubations <.001 1, [n (%)] 884 (97.2) 845 (98.5) 39 (76.5) 2, [n (%)] 23 (2.5) 13 (1.5) 10 (19.6) 3, [n (%)] 1 (0.1) 0 (0.0) 1 (2.0) 4, [n (%)] 1 (0.1) 0 (0.0) 1 (2.0)

Re-operation, [n (%)] 35 (3.9) 27 (3.1) 8 (15.7) <.001

Atrial fibrillation, 342 ( 37.6) 312 ( 36.4) 30 (58.8) .002 [n (%)]

Post-extubation repeat 21 (2.3) 18 (2.1) 3 (5.9) .108 ICU admission, [n (%)]

ICU stay 40.8 (50.2) 28.3 (46.8) 142.9 (97.5) <.001 [median (IQR)] (h)

Preoperative hospital 1.0 (1.0) 1.0 (1.0) 1.0 (3.0) .001 stay [median (IQR)] (days)

Postoperative hospital 7.0 (3.0) 7.0 (3.0) 15.0 (10.0) <.001 stay, [median (IQR)] (days)

Total inpatient stay, 8.0 (5.0) 8.0 (4.0) 16.0 (10.0) <.001 [median (IQR)] (days)

Note. ICU = intensive care unit; IQR = interquartile range.

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After exclusion of clinically redundant predictor variables, 26 variables were entered into the bootstrapping selection model. Of those, 13 were included in >10 % of the bootstrap resamples and were subsequently entered into the multivariate model (Table

3.5). Findings from logistic regression analysis identified the following independent predictors of dysphagia: intubation duration (p < .001; OR 1.93, 95 % CI 1.63–2.29) for every 12-h increment, age (p = .004; OR 2.12, 95 % CI 1.27–3.52) for every 10-year increment, and the occurrence of postoperative sepsis (p = .01; OR 14.03, 95 % CI 1.78–

110.72) with a model c-statistic of 0.94.

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Table 3.5

Independent predictors of postoperative dysphagia

Odds Variable p-value 95% CI Ratio Demographics Age 0.004 2.12a 1.27–3.52 Male 0.13 2.08 0.81–5.34

Pre-operative Characteristics Atrial fibrillationb 0.38 1.75 0.51–6.06

Chronic kidney diseasec 0.09 2.15 0.90–5.13 Congestive heart failure 0.51 1.41 0.51–3.89 Hypertension 0.44 0.69 0.27–1.78 Left main artery stenosis 0.33 1.62 0.62–4.26 Left ventricular dysfunction 0.62 1.32 0.44–3.95

Peri-/Post-operative Characteristics Intubation duration <.001 1.93d 1.63–2.29 MIe 0.23 0.44 0.12–1.66 Sepsisf 0.01 14.03 1.78–110.72 Strokeg 0.13 4.37 0.66–29.05 Valve surgery 0.36 1.57 0.59–4.15

Note. CI = confidence interval. a Point estimate based on ten year increments. b Preoperative atrial fibrillation or atrial flutter. c At least moderate chronic kidney disease as defined by estimated creatinine clearance of <60mL/min. d point estimate based on 12 hour increments. e preoperative myocardial infarction including Q-wave and Non-Q-wave infarctions. f peri/post-operative sepsis as defined by positive blood cultures. g peri/post-operative stroke.

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Discussion

This study is the first to report dysphagia frequency across stratified intubation durations after both coronary artery bypass and cardiac valve surgery. We determined that dysphagia frequency (1) is highest following intubation exceeding 48 h, (2) is negligible in those patients intubated for ≤12 h and (3) exceeds the cumulative population incidence previously reported (Ferraris et al., 2001; Hogue et al., 1995; Rousou et al.,

2000) in those intubated between 12 and 48 h. Most notably, our findings are the first to determine that the odds of a patient having dysphagia increase by a factor of 2 for every additional 12 h of endotracheal intubation or for every additional decade of age.

Similar to previous work, this study identified many pre- and perioperative risk factors associated with dysphagia as well as three independent predictors: advanced age

(Hogue et al., 1995), prolonged intubation (Barker et al., 2009; Hogue et al., 1995), and sepsis (Barker et al., 2009). While we also found that both pre- and perioperative stroke

(Barker et al., 2009; Rousou et al., 2000) as well as TEE use (Hogue et al., 1995; Rousou et al., 2000) were more common in those presenting with dysphagia, neither variable proved to be independently predictive of dysphagia in our study. Although TEE use was not predictive of dysphagia in our study, the frequency of dysphagia was more common in those patients who underwent valve surgery than those who underwent bypass. While some studies have reported higher gastrointestinal complications, including gastrointestinal ischemia and hemorrhage, following valve surgery (Bolcal et al., 2005;

D'Ancona et al., 2003), to our knowledge no study has compared the occurrence of oropharyngeal dysphagia in those who underwent bypass versus valve surgery. Although comparing the frequency of dysphagia between these two patient groups (valve vs.

RETROSPECTIVE STUDY 101 bypass) is outside the scope of this current study, we feel that it does warrant investigation in the future. While only speculative, this difference is likely multifactorial and may be related to the type of surgery or any number of other factors such as baseline cardiac function, pre-existing medical comorbidities, perioperative stroke, cardiopulmonary bypass time, inotropic support, or intubation duration.

The frequency of dysphagia across our entire sample is similar to that reported previously (Ferraris et al., 2001; Hogue et al., 1995; Rousou et al., 2000). Specifically, our results also confirm previously reported low frequencies for patients intubated ≤12 h

(Burgess et al., 1979). In addition, we confirmed that those patients intubated for >48 h were at the greatest risk of developing dysphagia; our dysphagia frequency for that intubation group was 67.5 %, a much higher frequency than previously reported (Barker et al., 2009). Although the study by Barker and colleagues was conducted at the same institution, patients in our study who had intubations >48 h were older and had greater

NYHA symptom class, suggesting a population at increased risk of complications.

Establishing the cause of dysphagia following endotracheal intubation is a challenge often due to patients’ medical complexity and their comorbidities. While determining causation is outside the scope of our current study, some have reported structural and mechanical alterations to the upper airway following extubation in those patients with dysphagia (Postma et al., 2007; Tolep et al., 1996). In addition, various intubation techniques and induction medication can either positively or negatively affect protective airway reflexes (Mencke et al., 2003).

Our study had limitations that were inherent in its retrospective nature. We were unable to investigate baseline swallowing status as well as rule out all pre-existing

RETROSPECTIVE STUDY 102 medical conditions that may predispose a patient to dysphagia such as neurological disorders (Martino et al., 2005). Our postoperative definition of dysphagia was also limited to bedside speech-language pathology assessment findings as well as surrogate nutrition variables such as modified texture diets or tube feeding as few patients received instrumental swallowing assessments. However, our identification of those with dysphagia was conservative. Specifically, we limited initial identification of dysphagia to within 96 h of final extubation, and most patients met multiple criteria for the presence of dysphagia. The dysphagic patients had adequate consciousness as assessed by the GCS scores and/or nursing records. We were unable to fully assess the presence of delirium as formal delirium screening scores were not recorded and they could not be derived from the available data. Finally, our data were limited to a single large, quaternary-care cardiac center serving a broad multiethnic demographic, suggesting but not proving that our findings would be applicable to similar centers. Limitations notwithstanding, we attempted to maintain methodological rigor, maximize generalizability and minimize bias in several ways: (1) developing a priori operational definitions of dysphagia and our descriptive intubation strata, (2) including a homogeneous patient sample typical of many

CV surgery centers, and (3) maintaining blinding throughout our data collection.

In conclusion, our description of dysphagia frequency, according to varying intubation durations in a CV surgery population, demonstrated that the highest risk of dysphagia occurs in patients intubated for more than 48 h. We identified risk factors associated with dysphagia as well as its independent predictors across the entire study sample. In general, older patients, those with perioperative sepsis, and longer intubation had the greater dysphagia risk. While further prospective studies are needed to determine

RETROSPECTIVE STUDY 103 perioperative or comorbid factors that affect dysphagia severity and/or recovery, the present findings will serve as an important first step in the identification of at-risk patients following extubation.

FEASIBILITY STUDY

CHAPTER IV

DYSPHAGIA INCIDENCE AND SWALLOWING PHYSIOLOGY FOLLOWING PROLONGED INTUBATION AFTER CARDIOVASCULAR SURGERY: A FEASIBILITY STUDY

Abstract

Dysphagia incidence following prolonged intubation after cardiovascular (CV) surgery, although common (>50%), has never been determined prospectively with the population’s swallowing physiology largely unknown. As a first step, our primary objective was to assess feasibility and patient acceptance of tests used to evaluate swallowing physiology following prolonged intubation after cardiovascular surgery.

From July-October 2011, all consecutive adults undergoing CV surgery at our institution who were intubated >48 hours were approached to participate. Patients with tracheostomies were excluded. Enrolled patients underwent a videofluoroscopic swallowing study (VFS) and nasendoscopy within 48 hours after extubation. VFSs were interpreted using ratings scales (Modified Barium Swallow Measurement Tool for

Swallow ImpairmentTM© and Penetration Aspiration Scale) and objective physiological measurements (hyoid displacement and pharyngeal constriction ratio). Two independent raters blinded to clinical data completed physiological measurements. Feasibility parameters included: recruitment rate, patient participation, task completion durations and the inter-rater reliability of VFS measures. Upon study completion, participants completed self-administered impact questionnaires. Of the 39 patients intubated for >48h,

16 met eligibility criteria. Three were enrolled and completed the VFS. All refused nasendoscopy. VFS completion time ranged from 14 minutes to 52 minutes with item interrater reliability ranging from .25 (95% CI: -.10-.59) to .99 (95% CI: .98-.99).

Participants reported minimal study burden. Oral and pharyngeal swallow abnormalities

104

FEASIBILITY STUDY 105 were observed across all patients. This study design was not feasible. Recruitment was slow, few patients participated and no patient agreed to all procedures. We discuss necessary methodological changes and lessons learned for future research.

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Introduction

Dysphagia occurs in approximately half of all patients who are intubated for 48 hours or more following cardiovascular (CV) surgery (Barker et al., 2009; Skoretz et al.,

2014). Not only does post-extubation dysphagia increase hospitalization costs (Ferraris et al., 2001); patients with the disorder are at greater risk of pneumonia, reintubation, and death (Macht et al., 2011).

What is known about dysphagia frequency and swallowing physiology following prolonged intubation after CV surgery is limited by study design and the quality of the available literature (Skoretz, Flowers, et al., 2010). The reported dysphagia incidence is questionable given these intrinsic study limitations which include retrospective design, variable diagnostic methods, inconsistent use of instrumental assessments across enrollees and lack of assessor blinding (Skoretz, Flowers, et al., 2010). In addition, while most studies report on dysphagia associated risk factors (Skoretz, Flowers, et al., 2010), the few that have characterized the swallowing impairment (Barker et al., 2009; Burgess et al., 1979; Ferraris et al., 2001; Harrington et al., 1998; Hogue et al., 1995; Partik et al.,

2003) have done so using: instrumental assessment methods with low sensitivity and specificity (Burgess et al., 1979; Harrington et al., 1998), general dysphagia terminology

(Barker et al., 2009; Ferraris et al., 2001; Harrington et al., 1998), assessments focusing on only aspiration (Burgess et al., 1979; Harrington et al., 1998), a mixed adult and pediatric patient sample (Partik et al., 2003) or without using operationally defined swallowing outcomes (Hogue et al., 1995). To date two studies have reported on swallowing characteristics beyond aspiration and general pharyngeal impairment (Hogue et al., 1995; Partik et al., 2003), yet no study has analyzed the swallowing physiology

FEASIBILITY STUDY 107 using standardized rating scales or objective physiological measurements. Hence, the mechanisms underlying dysphagia in this population are yet to be determined.

Presently, there are two psychometrically validated tools designed to rate the swallow captured on videofluoroscopy: the Modified Barium Swallow Measurement

Tool for Swallow Impairment (Martin-Harris et al., 2008) (MBSImpTM©, Northern

Speech Services, Gaylord, MI) and the Penetration-Aspiration Scale (Rosenbek et al.,

1996) (PAS). The MBSImpTM© is comprised of 17 different components that collectively describe oral, pharyngeal and esophageal function. The PAS is an 8-point interval scale that describes the degree to which material has invaded the airway and whether the material has been ejected. Together, the MBSImpTM© and PAS quantify swallowing impairment severity and airway protection respectively.

While the MBSImpTM© and PAS rate aspects of the patient’s swallow, they do not objectively measure structural movement during the swallow. Individual videofluoroscopic images can be extracted from the videofluoroscopic swallow study

(VFS) and used to conduct targeted objective physiological measurements such as hyoid bone displacement (Leonard, 2007; Leonard et al., 2000; Molfenter & Steele, 2014;

Steele et al., 2011) and pharyngeal constriction (Leonard, 2007; Leonard et al., 2000).

Adequate hyoid elevation (Jacob et al., 1989; Kim & McCullough, 2008; Leonard, 2007;

Steele et al., 2011) and pharyngeal constriction (Leonard, 2007; Leonard et al., 2009;

Setzen et al., 2003; Yip et al., 2006) are associated with successful propulsion of food or fluid through the pharynx into the esophagus thereby preventing laryngeal penetration, tracheal aspiration and/or pharyngeal residue. Recently extubated patients are at increased risk of reduced hyoid elevation as well as impaired pharyngeal constriction due

FEASIBILITY STUDY 108 to the relative inactivity of oropharyngeal musculature during endotracheal intubation and at present this has never been investigated. In addition, these displacement measures are useful to clinicians when designing treatment programs for patients with dysphagia.

While the VFS is widely accepted as a gold standard instrumental technique to assess the swallow, it is not the diagnostic tool of choice when ruling out oropharyngeal and laryngeal pathologies. Regardless of the underlying medical etiology, intubation and presence of the artificial airway can lead to mucosal abnormalities, laryngeal edema, granulomas and vocal fold immobility which can affect the anatomical integrity and physiology of the swallow (DeVita & Spierer-Rundback, 1990; Postma et al., 2007;

Thomas et al., 1995; Tolep et al., 1996). Nasendoscopy provides a direct view of the hypopharynx and larynx, along with the superior aspects of the upper trachea and upper esophageal sphincter, providing diagnostic information not otherwise acquired with videofluoroscopy (Langmore et al., 1988; Langmore et al., 1991; Murray et al., 1996).

Together, these diagnostic techniques provide a comprehensive assessment of the swallow and the structures involved; however, these tests are lengthy, invasive and may not be tolerated by this patient population. As a result, the feasibility of using these instrumental approaches on patients following prolonged intubation after CV surgery needs to be determined.

Our primary objective was to determine the feasibility of using these instrumental assessments in order to assess swallowing and upper airway physiology prospectively on consecutively enrolled CV surgery patients following prolonged intubation. Our secondary objective was to explore the tolerability and impact of this study on patients and nursing. These findings will be used to inform a future large-scale study to

FEASIBILITY STUDY 109 systematically evaluate the incidence of dysphagia and formally assess the swallowing physiology of this patient population.

Methods Participants

From July 1 to October 31 2011, all consecutive patients intubated for >48 hours following CV surgery at our institution were approached for study participation. Eligible patients included those >18 years of age who were extubated within the previous 48 hours. We excluded patients with a history of dysphagia, tracheotomy, head/neck cancer, or neurological disorders including stroke or seizures. Also excluded were patients deemed inappropriate for study participation by the attending medical team, including those with reduced consciousness, medical instability or who were nil per os (NPO) due to gastroenterologic complications. Our institutional research ethics board approved this study and all participants provided written informed consent prior to participation. If the patient was unable to provide research consent, the patient’s surrogate decision maker was approached for consent on the patient’s behalf.

Study Process

Within 48 hours from time of extubation, the patient’s swallow was assessed using a VFS conducted by a speech-language pathologist blinded to all clinical data. In addition, these patients were given the option to undergo flexible nasendoscopy by otolaryngology. At the completion of instrumental testing, we invited the patient and attending nurse to provide anonymous feedback on the study process using a self- administered impact questionnaire. We measured feasibility throughout the study using process and resource parameters including: recruitment rate, number of eligible patients,

FEASIBILITY STUDY 110 losses to enrollment, patient participation with the instrumental protocols, task completion times and the inter-rater reliability of the VFS measures.

Videofluoroscopic Swallow Study

Imaging. Fluoroscopy was conducted using a Toshiba Ultimax System MDX-

8000A (Toshiba America Medical Systems Inc., Tustin, CA) in the lateral position.

Using continuous pulse, the image was captured in uncompressed form using a TIMS

2000 DICOM system (Forest Imaging, Chelmsford, MA) at a rate of 30 frames per second. Image collimation allowed for views of the anterior lip margins, superior aspect of the nasal passages, posterior margins of the cervical vertebrae, and cervical esophagus.

A visible scalar with known dimensions (a quarter) was placed submentally in the image field for calibration of image magnification.

Videofluoroscopic swallow study procedure. Each patient was presented with various fluid and food textures combined with E-Z-EM barium contrast agents (E-Z-EM

Inc., Lake Success, NY) according to institutional standard practice and preparation. The trials were presented as follows: 1) thin liquid with diluted liquid Polibar Plus barium sulfate suspension (47% w/v; 3 x 5-ml boluses by spoon, 2 x 15-ml boluses by cup), 2) applesauce mixed with powdered barium (28% w/w; 3 x 5-ml boluses by spoon), 3) ½

Peak Frean digestive cookie coated with barium paste (60% w/w) and 4) sequential cup sips of the thin liquid barium dilution (47% w/v; 100-ml maximum). This sequence was discontinued as soon as patient safety was a concern. For all trials, except for sequential cup sipping, a cue-swallow command was used with instruction to hold the bolus in the oral cavity and then swallow on command.

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Videofluoroscopic Swallow Study Measures

Following VFS completion, we conducted two types of analyses: i. standardized

VFS assessment tools and ii. objective physiological displacement measurements.

Standardized VFS assessment tools. Each VFS was scored in its entirety using two standardized, validated and reliable tools: the Modified Barium Swallow Impairment

Profile (MBSImpTM©, Northern Speech Services, Gaylord, MI) (Martin-Harris et al.,

2008) and the Penetration Aspiration Scale (PAS) (Rosenbek et al., 1996).

One rater (SAS), while blinded to clinical data, completed the MBSImpTM© for each bolus administration. The MBSImpTM© is a standardized tool used to quantify severity of oral and pharyngeal impairment through assessment of 17 physiologic components. Each component has a rank-ordered scoring system, ranging from a three to five point scale, with increasing scores indicating greater impairment. A priori we excluded two components, pharyngeal constriction and esophageal clearance, the former, as it requires an anterior posterior fluoroscopic view, which cannot be obtained from this patient population given their restricted mobility at the time of testing, and the latter as it was beyond the scope of this study. Table 4.1 summarizes the components included in this study along with their scoring ranges. The MBSImpTM© rater completed the

MBSImpTM© certification process. This process included a minimum of 21 training hours and subsequently required a minimum of 80% reliability during accuracy testing of the

MBSImpTM© physiologic components.

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Table 4.1.

MBSImpTM© oral and pharyngeal componentsa

Component Scale Abbreviation

Oral 1 Lip closure (0-4) LipC 2 Tongue control during bolus hold (0-3) TC 3 Bolus preparation/mastication (0-3) BP 4 Bolus transport/lingual motion (0-4) BT 5 Oral residue (0-4) OR 6 Initiation of pharyngeal swallow (0-4) IPS

Pharyngeal 7 Soft palate elevation (0-4) SPE 8 Laryngeal elevation (0-3) LE 9 Anterior hyoid excursion (0-2) HM 10 Epiglottic movement (0-2) EM 11 Laryngeal vestibule closure (0-2) LVC 12 Pharyngeal stripping wave (0-2) PSW 14 Pharyngoesophageal segment opening (0-3) PESO 15 Tongue base retraction (0-4) TBR 16 Pharyngeal residue (0-4) PR

Note. a Components 13 (Pharyngeal constriction) and 17 (Esophageal clearance) excluded a priori.

Two independent raters (SAS and RM) blinded to each other and all clinical data conducted PAS scoring for each bolus administration. The PAS (Rosenbek et al., 1996) is an 8-point scale that scores the depth of airway invasion by the fluid or food bolus, whether it is expelled from the airway as well as any patient reaction (Table 4.2).

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Table 4.2.

Penetration-Aspiration Scale (Rosenbek et al., 1996)

Score Description

1 Material does not enter the airway

2 Material enters the airway, remains above the vocal folds, and is ejected from the airway

3 Material enters the airway, remains above the vocal folds, and is not ejected from the airway

4 Material enters the airway, contacts the vocal folds, and is ejected from the airway

5 Material enters the airway, contacts the vocal folds, and is not ejected from the airway

6 Material enters the airway, passes below the vocal folds and is ejected into the larynx or out of the airway

7 Material enters the airway, passes below the vocal folds, and is not ejected from the trachea despite effort

8 Material enters the airway, passes below the vocal folds, and no effort is made to eject

Displacement measurements. Two independent raters (SAS and RM) blinded to each other and all clinical data, conducted frame selection and displacement measurements for each 5-ml and 15-ml bolus using ImageJ (National Institutes of Health,

Bethesda, MD) focusing on two domains: hyolaryngeal excursion and pharyngeal constriction.

Hyoid excursion during each swallow was calculated according to two techniques: 1) as an absolute trajectory measurement in millimeters (mm) quantifying the anterior-superior displacement of the hyoid bone from its rest position (Leonard, 2007;

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Leonard et al., 2000) and 2) as an internally scaled calculation of separate anterior and superior hyoid movement using the patient’s cervical vertebrae as a reference (Steele;

Steele et al., 2011). We utilized two fluoroscopy images per bolus for each technique: one with the hyoid at rest and one at maximal anterior-superior displacement. The hyoid

“rest” frame was defined differently for each: 1) during bolus hold prior to swallow initiation for the absolute measurements and 2) during lowest hyoid position following swallow completion for the scaled measurements. Frame selection, anatomical tracing specifications, and displacement calculations for both techniques were completed according to previously published methods (Leonard, 2007; Leonard et al., 2000; Steele;

Steele et al., 2011).

We measured pharyngeal constriction during the swallow using ImageJ through a pharyngeal constriction ratio calculation (PCR)(Leonard, 2007; Leonard et al., 2009;

Leonard et al., 2000). For this measurement, we defined the bolus hold frame (PAHOLD) as the hold during the 5-ml thin liquid bolus. The maximum pharyngeal contraction frames (PAMAX) were defined as the frame with maximal pharyngeal contraction during each of the following: 5-ml and 15-ml thin liquid and 5-ml pureed boluses. Following pharyngeal space tracing for each frame, we calculated the pharyngeal constriction ratio

2 by dividing the pharyngeal area (cm ) of the selected frames (PAMAX/PAHOLD)(Leonard,

2007; Leonard et al., 2009; Leonard et al., 2000).

Study Impact Questionnaires and Patient Variables

Following VFS completion, the patient and attending nurse were asked to complete study impact questionnaires. The questionnaires (Table 4.3) utilized a 5-point

Likert scale rating patient comfort, study impact on nursing workload and perceived

FEASIBILITY STUDY 115 study value while providing an open-ended section for comments. Once completed, we instructed the patient and/or nurse to deposit their questionnaire in a locked box on the hospital unit. Following unblinding, the first author (SAS) recorded patient variables such as demographics (age, gender) and operative information (surgery type, intubation duration).

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Table 4.3.

Survey questions

Respondent Question Rating Scale

Easy Somewhat Somewhat Very How did you find the x-ray swallow test? Adequate easy difficult difficult

Overall, how was your experience with this Easy Somewhat Somewhat Very A. Patient Adequate research? easy difficult difficult

Somewhat Somewhat Very How was this form to complete? Easy Adequate easy difficult difficult

In your opinion, to what degree did this study affect Not at all Very little A little Somewhat A lot the delivery of patient care?

How did the participation of this study fit into your Somewhat With With great Easily Adequately daily tasks? easily difficulty difficulty B. Nurse How were you able to accommodate being part of Somewhat With With great Easily Adequately the videofluoroscopic swallow study? easily difficulty difficulty

Somewhat Somewhat Very Easy Adequate How was this form to complete? easy difficult difficult

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Scoring and Statistical Analyses

For each patient, we scored each bolus administration individually with both the

MBSImpTM© and PAS according to published guidelines (Martin-Harris et al., 2008;

Rosenbek et al., 1996), if a texture or bolus volume was not administered to a patient secondary to safety concerns, the patient received the highest, thereby most impaired,

MBSImpTM© and PAS score for that trial (Martin-Harris et al., 2008). For each patient, we derived overall impression scores (OI) for each of the MBSImpTM© components according to published standards, namely using the patient’s worst score for each component regardless of texture or volume (Martin-Harris et al., 2008). We derived the total oral impairment (components 1-6) and total pharyngeal impairment (components 7-

12, 14-16) scores for each patient by the summation of each OI score from the appropriate oral and pharyngeal components. We dichotomized PAS scores as either normal (PAS scores < 2) or abnormal (PAS scores ≥ 3) for each bolus administration

(Allen et al., 2010; Daggett, Logemann, Rademaker, & Pauloski, 2006) and summarized these data as frequency counts.

We reported displacement measurements as medians and interquartile ranges

(IQR) according to bolus volume and texture. We calculated the single measures interobserver agreement using absolute agreement two-way mixed intraclass correlation coefficient (ICC) for both frame selection and displacement measurements. We reported the approximate duration in minutes for patient transport, patient study participation and task completion (VFS preparation, study archiving, frame selection, displacement measurements, MBSImpTM© and PAS scoring). We summarized questionnaire responses descriptively and according to frequency counts. Statistical analyses were conducted

FEASIBILITY STUDY 118 using IBM SPSS version 22 (IBM Corporation, Armonk, NY). Radar plots were created using OriginPro 9.1 (OriginLab Corporation, Northampton, MA) and scatter plots were created using GraphPad Prism 6 (GraphPad Software Inc., La Jolla, CA).

Results

Patient Recruitment and Characteristics

During the four-month study period, 39 patients required intubation for more than

48 hours (Figure 4.1). Of those, 16 met the inclusion criteria with three patients agreeing to participate for an approximate recruitment rate of one patient every five weeks. Of the remaining 13 patients, six declined participation, six were not approached for participation due to institutional and operational restrictions (i.e., weekend extubation and diagnostic imaging suite downtime), and one was transferred off-service.

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Intubated >48h: N = 39

Did not meet inclusion criteria: n = 23 • Exclusion diagnoses: n = 10

• Expired: n = 6 • Tracheotomy: n = 7

Unable to enroll: n = 13 • Imaging restrictions: n = 2 • Weekend extubation: n = 4

• Patient transfer: n = 1 • Declined participation: n = 6

Enrolled: N = 3

Figure 4.1. Study enrollment.

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Our consecutive case series consisted of two males and one female aged 71, 37, and 71 years respectively. Intubation durations ranged from 49 to 82 hours with all patients undergoing an atraumatic intubation and extubation as documented by the attending anaesthesiologist. Participant characteristics are summarized in Table 4.4. At the time of study participation, all patients were in intensive care requiring 24-hour one- to-one nursing care. All enrolled patients refused the nasendoscopy procedure.

Table 4.4.

Patient characteristics

Case Demographics Operative Variables

Intubation Sex Age Surgery type (yrs) duration (h)

P1 M 71 Heart transplant 53.3

P2 M 37 Aortic valve replacement 49.3 Tricuspid valve repair

P3 F 71 Coronary artery bypass 82.5

Note. yrs = years; h = hours.

Videofluoroscopic Swallow Study

The videofluoroscopic swallow study (VFS) was completed 30, 25, and 37 hours following extubation on patients 1, 2, and 3 respectively. All consistencies and volumes were administered to patients 1 and 2, with patient 2 requiring two mouthfuls for the ½ digestive cookie. For patient 3, the VFS protocol was discontinued following two of the three pureed (5-ml) boluses. Patients 1 and 3 were administered an additional thin fluid

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(5-ml) bolus secondary to technical difficulties. For these patients, the first thin fluid bolus (5-ml) was not included in the analyses. After this exclusion, total of 11, 10, and 5 boluses were included in the analyses for patients 1, 2, and 3 respectively. All patients were NPO prior to the VFS. Artifacts on the radiographic image included a central line

(patients 1 and 2) and an in-situ nasogastric feeding tube (patient 3).

For each VFS, patient preparation and transport to and from the fluoroscopy suite ranged from 30 to 60 minutes. Prior to patient arrival, room and equipment preparation required an average of ten minutes. While in the imaging suite, patient setup and the

VFS were completed within 15 minutes. Following the completion of each VFS, data transfer and study archiving took approximately one hour. A total of three study personnel were involved in the VFS directly: an x-ray technician, a speech-language pathologist (SAS) and a research coordinator. The patient’s nurse and clinical speech- language pathologist were also in attendance.

Videofluoroscopic measures. Videofluoroscopic measurements were completed for all 3 patients. The time to complete frame selection and measurement for each method ranged from less than two minutes to six minutes per bolus administration. The total time to complete each measurement ranged from 14 minutes to 52 minutes for each

VFS. Each VFS measure and its corresponding task completion time and inter-rater reliability (as applicable) are summarized in Table 4.5.

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Table 4.5.

Task completion time and interrater reliability according to VFS measure

VFS Measure Completion Time (min) ICC (95% CI)

Per bolus Frame Per VFS Measurement administration selection

MBSImpTM© 6 52 N/A N/A

PAS <2 17 N/A .92 (.83-.96)

Absolute hyoid 5 35 .99 (.98-.99) .90 (.76-.96) displacementa Scaled hyoid <2 14 .98 (.96-.99) .26 (-.05-.52) displacementa Pharyngeal 5 35 .99 (.98-.99) .25 (-.10-.59) constrictiona

Note. VFS = videofluoroscopic swallow study; min = minutes; CI = confidence interval; MBSImpTM© = Modified Barium Swallow Impairment Profile; N/A = not applicable; PAS = Penetration Aspiration Scale. a displacement measurements conducted on 5-ml and 15-ml bolus volumes only.

Standardized VFS assessment tools. Patient 3 received the maximum overall impression (OI) score across all individual MBSImpTM© oral and pharyngeal components

(Figures 4.2a and 4.2b). As a result, patient 3 received the highest total oral and total adjusted pharyngeal scores of 22 and 26 respectively, exhibiting the most severe swallowing impairment of all patients in our case series. Of the two remaining patients, patient 1 received a total oral impairment score of nine as compared to three for patient 2, with greater impairment on: lip closure, bolus preparation, bolus transport and the initiation of the pharyngeal swallow. Conversely, patient 2 received a total pharyngeal impairment score of six as compared to five for patient 1, with greater impairment on

FEASIBILITY STUDY 123 laryngeal vestibule closure and pharyngeal stripping wave components. Of the remaining pharyngeal components, patients 1 and 2 differed only on tongue base retraction with OI scores of two and one respectively. Of the oral components, all three patients exhibited impairment on oral residue and initiation of the pharyngeal swallow. Additionally, all patients exhibited impairment on the following pharyngeal components: pharyngoesophageal segment opening, tongue base retraction and pharyngeal residue.

Patient 1 Patient 2 Patient 3

Figure 4.2a. MBSImpTM© oral components across patients.

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Patient 1 Patient 2 Patient 3

Figure 4.2b. MBSImpTM© pharyngeal components across patients

Regardless of texture, volume or paradigm (i.e. cued versus spontaneous swallow), patients 1 and 2 had normal airway protection on all swallows (a PAS score of

≤ 2). We observed abnormal airway protection across all bolus administrations with patient 3 (a PAS score of ≥ 3). Clinically, patients 1 and 2 began regular texture diets following VFS completion while patient 3 remained NPO with enteral feeding via nasogastric feeding tube.

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Displacement measurements. Hyoid displacements are presented in Table 4.6.

Patient 3 presented with the smallest median (IQR) absolute hyoid displacement

(Leonard, 2007; Leonard et al., 2000): 8.3mm (2.3) and 8.3mm (1.7) with thin (5-ml) and pureed (5-ml) textures respectively. For the same bolus textures and volume, patient 1 had the largest median (IQR) displacements: 12.7mm (1.7) and 14.8mm (2.1) respectively. Absolute displacement median values increased with both increasing volume as well as increasing texture viscosity for patients 1 and 2 whereas median values for patient 3 remained consistent regardless of stimulus change. Scaled anterior and superior hyoid displacement measurements (%C2C4 units) (Steele et al., 2011) were similarly patterned with: 1) smallest median values regardless of texture for patient 3 and

2) largest median values for patient 1 with thin fluid boluses.

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Table 4.6.

Hyoid displacement measurements according to patient

Case Absolute Hyoid Displacement Scaled Hyoid Displacement (mm) (%C2-C4 units)

Anterior hyoid displacement Superior hyoid displacement

Thin liquid Pureed Thin liquid Pureed Thin liquid Pureed

5ml 15ml 5ml 5ml 15ml 5ml 5ml 15ml 5 ml

P1 12.7 (1.7) 14.2 (3.2) 14.8 (2.1) 41.6 (18.7) 52.4 (6.0) 40.8 (30.7) 18.5 (25.8) 31.0 (10.9) 36.9 (25.9)

P2 9.8 (1.8) 9.8 (1.6) 9.9 (2.1) 23.1 (41.0) 27.4 (8.1) 24.3 (9.4) 27.9 (57.8) 33.6 (17.0) 36.7 (30.8)

P3 8.3 (2.3) NT 8.3 (1.7) 17.9 (12.2) NT 22.5 (5.8) 13.9 (14.5) NT 17.8 (9.5)

Note. Values are reported as median (IQR), mm = millimeter; ml = milliliter; NT = not tested; IQR = interquartile range.

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When comparing PCR measurements across patients according to bolus texture and

volume (Figure 4.3), we measured the smallest median (IQR) pharyngeal constriction ratio with

thin fluid boluses (5-ml) for patient 1 (.02 [.03]) and the largest with patient 3 (.09 [.09]) for the

same bolus texture and volume. Within patients across bolus texture and volumes, PCR values

decreased with increasing viscosity for patients 2 and 3 with the inverse measured for patient 1.

Figure 4.3. Pharyngeal constriction ratio by patient according to bolus texture and volume.

Study Impact Questionnaires

Patient comfort questionnaires. One patient completed the patient comfort questionnaire. Ratings were “adequate” for VFS and overall study participation and “easy” for questionnaire completion. This patient would have preferred more information during the consent process about the instrumental assessment. Of the two remaining patients, one was medically incapable of completing the questionnaire and one was discharged prior to questionnaire completion.

Workload impact questionnaires. All attending nurses, three CVICU nurses and one nursing student, completed the workload impact questionnaire. All nurses reported the study fit

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well with daily tasks and the majority felt VFS accommodation was “easy” or “adequate”. Half of the nurses reported the study’s impact on patient care delivery was minimal. Nursing suggestions for study modifications included: 1) further advance notice regarding the procedure timing in order to allow ample time to ready the patient for transport and 2) regular confirmation with nursing staff regarding the patient’s hemodynamic stability and inotropic support requirements prior to scheduling transport.

Discussion

Our study as designed was not feasible. As a result, this experience has afforded us the opportunity to revisit our methodology prior to conducting a larger study. While we were able to enroll participants prospectively with the aim to conduct an instrumental swallowing assessment within 48 hours after extubation following cardiovascular surgery, the rate of enrollment was low and none of the enrolled patients agreed to all procedures. We had poor response rates on patient impact questionnaires. In contrast, all nurses completed their impact questionnaires. They rated our study protocol as “easy to accommodate” and without significant impact on workflow. Also, all enrolled patients underwent the VFS procedure, therefore making our study the first to describe swallowing physiology on consecutively enrolled, recently extubated patients following

CV surgery using psychometrically validated and objective measures.

We took great lengths to maximize the methodological rigor of this study. We recognize that this may have negatively impacted patient enrollment and study feasibility, but it permitted us to contrast our study with previous work which may have favored ease of study conduct over maximized rigor. We minimized bias risk through: consecutive enrollment, conducting the same instrumental assessment on all patients, and assessor blinding both to each other and clinical data throughout the study. Our findings have shown us that for a successful future large-scale study

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with the objectives of determining dysphagia incidence prospectively and assessing swallowing

physiology, it will be important to consider changes in design. Following our experiences, we

propose diagnostic methods and interpretation measures more suited to investigating swallowing physiology in this population with the goals of increasing enrollment rate and minimizing impact on patients while ensuring study rigor.

Although we enrolled a limited number of patients during the study’s four-month duration, we were able to target the patient group at the highest risk of developing dysphagia

(Barker et al., 2009; Skoretz et al., 2014). In order to meet a hypothetical sample size of 100 patients however, it would take over ten years to complete the study at this enrollment rate at a single institution. Increasing the number of eligible patients can be met through: 1) including patients intubated for durations greater than 24 rather than 48 hours, 2) reducing the number of patients lost to enrollment and 3) expanding the study to include multiple centers. First, expanding the prolonged intubation definition to include durations exceeding 24 hours would continue to capture at-risk patients (Skoretz et al., 2014). In a recent study conducted at the same institution stratifying patients following CV surgery according the various intubation durations

(Skoretz et al., 2014), the authors demonstrated that dysphagia frequencies following intubation durations of 24-48 hours were the second highest, approximately 17%, second only to those intubated for more than 48 hours. Second, eligible patients extubated over the weekend accounted for 25% of our losses to enrollment. These losses could be minimized through increasing research staff availability over weekends or increasing the post-extubation instrumental assessment window from 48 to 72 hours. Third, including other centres similar to ours would increase the number of available patients meeting our eligibility criteria.

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These study changes are not without caveats. While including multiple sites or

conducting weekend assessments would require additional research staff thereby accruing

additional study costs, increasing the post-extubation instrumental assessment window could be problematic for study objectives namely 1) determining dysphagia incidence and 2) comparing swallow outcomes across the sample. First, swallowing physiology changes rapidly following extubation and as a result, there may be great variability across the sample. Two studies have reported on serial swallowing examinations following extubation: one reporting swallowing latencies in critical care patients (de Larminat et al., 1995) and the other on aspiration frequency following coronary artery bypass grafting (Burgess et al., 1979). De Larminat and colleagues

(de Larminat et al., 1995) found swallowing delays resolved within 48 hours. Similarly, Burgess and colleagues (Burgess et al., 1979) reported decreasing aspiration frequency from 33% to 20% to <1% following assessments conducted immediately, at four hours and eight hours post-

extubation respectively. Second, prior to swallowing outcome comparisons, a broader range in

post-extubation assessment times would require patient stratification according to assessment

completion time. As a result, a larger sample size may be required.

Although all nursing staff responded to our impact questionnaires, only one patient

completed theirs. This limits our ability to make inferences regarding patient impact, however,

we will use the respondent`s data to improve the consenting process. In addition, all patients

refused nasendoscopy. This suggests altering the study protocol to include only one instrumental

procedure. The research ethics board disallowed enquiry regarding participant refusal rationale

throughout the study, therefore we are unable to determine if patients would still enroll if

nasendoscopy were a stand-alone assessment. In regards to the nursing respondents, all felt

study participation fit well with their daily tasks. However they were equally divided on the

FEASIBILITY STUDY 131 degree to which study participation impacted the delivery of patient care. Their comments focused on timing issues with regards to patient preparation for and transport to radiology.

These issues may be resolved through an instrumental swallowing assessment conducted at the bedside.

Even though all patients refused nasendoscopy in a paradigm that also included VFS, an instrumental swallowing assessment that can be conducted in the ICU (e.g., fiberoptic endoscopic evaluation of swallowing [FEES]) may be more appealing to both patients and nurses. It may reduce the study’s impact on patients, nurses and operational resources as it would: 1) eliminate patient transport outside of ICU, 2) reduce the number of staff required to complete the instrumental assessment and 3) eliminate the use of a diagnostic imaging suite.

Since FEES is conducted at the bedside, it may be easier to schedule the procedure around other diagnostic procedures that patients must undergo while in the ICU. It can be conducted solely by a speech-language pathologist trained in the procedure with an otolaryngologist present or with them reviewing the recorded assessment at a later date. Not only does FEES involve fewer staff than VFS, it is arguably more sensitive in identifying events such as aspiration and pharyngeal residue (Kelly et al., 2007; Kelly et al., 2006). While this procedure offers the added benefit of direct visualization of oropharyngeal and laryngeal mucosa and secretions (Langmore et al.,

1988; Langmore et al., 1991; Murray et al., 1996), FEES also has its limitations. Due to the position of the scope in the oropharynx, this technique eliminates an oral functional assessment.

In addition, the view of the larynx and upper trachea is obliterated during the swallow due to soft palate elevation and pharyngeal constriction. As a result, airway penetration or aspiration occurring at that time cannot be observed. Currently, it also lacks psychometrically validated methods for interpretation or objective kinematic measurement techniques.

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Previously unreported for this patient population, the MBSImpTM© and PAS together provided a thorough standardized description of swallow function for each patient in our case series. Commensurate with the detailed impairment information acquired while using the

MBSImpTM© for each patient, we found the certification process and scoring method in our study required a substantial time commitment. While this time commitment may be reasonable for our research objectives, conducting MBSImpTM© component scoring for each bolus administration may not be clinically feasible.

According to the MBSImpTM©, all three patients exhibited some degree of impairment in the areas of oral and pharyngeal clearance, pharyngeal swallow initiation, tongue base retraction and pharyngoesophageal segment opening. In addition, two of the three patients also showed impairment on the following: lip closure, bolus preparation, bolus transport, pharyngeal stripping wave and laryngeal vestibule closure. Similar impairments have been reported in other studies

(Hogue et al., 1995; Partik et al., 2003). For example, Hogue and colleagues (1995) reported impaired oral function in 22% of patients along with impaired swallowing reflex in 67% and decreased pharyngeal peristalsis in 56%. In a study by Partik and colleagues (2003), they described tongue impairment in 27% of patients, along with impaired pharyngeal reflex trigger and/or pharyngeal weakness in 46% and upper esophageal sphincter dysfunction in 14%. In contrast, airway compromise occurred infrequently in our study when compared to previous publications. Only one of the three patients exhibited abnormal airway protection in our study whereas the number of patients aspirating ranged from 59% (Partik et al., 2003) to 90% (Hogue et al., 1995) previously.

To the best of our knowledge, we are the first to report on swallowing kinematics on recently extubated patients following CV surgery. The time required to complete the

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displacement measurements ranged from 14 to 35 minutes for each VFS. Of all the

measurements, scaled hyoid displacement required the least time to complete. By virtue of using scaled units when comparing measurements across patients, this method mitigates possible confounds such as sex and “size-of-system” differences (Molfenter & Steele, 2014). Therefore,

if significant differences are found using this technique, they may be more likely due to differing

physiology. As a result, this method may prove to be beneficial when investigating what factors

influence physiological differences in this patient population. When comparing interrater

agreement across all displacement measures, the reliability for frame selection across all

measures and absolute hyoid displacement measurement was excellent (Shrout & Fleiss, 1979).

In contrast, the reliability was poor for both scaled hyoid displacement measurement as well as

pharyngeal constriction ratio. Due to the anatomical location of a radiographic artifact on each

patient either along the cervical spine (i.e., central line) or in the pharynx (i.e., nasogastric tube),

it is likely that these measures were most susceptible to their presence thereby accounting for the

high variability between raters. While the published intra- and interrater reliabilities for these

methods are good to excellent (Leonard et al., 2000; Molfenter & Steele, 2014; Steele et al.,

2011), it is likely that these displacement measurement methods were designed and tested

primarily using subjects other than those in intensive care. Regardless, it is our opinion that

hyoid displacement and pharyngeal constriction measures are necessary for this population due

to the relative inactivity of the pharyngeal and laryngeal musculature during intubation and its

potential effect on swallow function (DeVita & Spierer-Rundback, 1990; Postma et al., 2007;

Thomas et al., 1995; Tolep et al., 1996). Ultimately, the reliability will need to be addressed

prior to their implementation in a larger study.

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Although we were unable to conduct any inferential statistical analyses due to our small

study sample, we were able to observe swallowing performance patterns across patients and VFS

measures. For example, the patient exhibiting the highest score on the PAS presented with the

smallest median hyoid displacement measurements with both the absolute and scaled measures

and largest median pharyngeal constriction ratios. Similarly in other populations, patients

exhibiting abnormal airway protection have reduced hyoid displacement measurements (Steele et

al., 2011) and a greater pharyngeal constriction ratio (Yip et al., 2006). Another pattern was

observed. Across patients, increasing MBSImpTM© impairment ratings on the anterior hyoid

displacement, pharyngeal stripping and laryngeal vestibule closure components corresponded

with smaller hyoid displacement, larger PCR measurements and abnormal airway protection

respectively. For example, the patient with the most impairment on the anterior hyoid

displacement MBSImpTM© component had the smallest hyoid displacement measurement.

Similarly, the patient with the highest impairment on the pharyngeal stripping wave component

had the largest PCR measurement. However due to our limited enrollment and poor inter-rater

reliability on some measures, our swallowing outcomes are unlikely to representative of this

patient population and must be interpreted with caution.

This feasibility study, which by definition is descriptive and exploratory in nature, has

several limitations. Not only was this study conducted for a very limited duration, it was

conducted at a single institution with limited enrollment thereby restricting generalizability of

our findings to other clinical sites. Due to our limited enrollment, we were unable to report

dysphagia frequency, and the swallowing characteristics we explored are unlikely to be representative of this population as whole. In addition our small sample size precluded statistical

comparisons of our VFS measures both within and across patients. While our study exclusions

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restricted etiologies that may cause pre-operative dysphagia, our patients’ pre-surgical

swallowing function was unknown. Although we analyzed our VFS using objective and

validated measures, our methodological differences throughout our VFS protocol, including

bolus volume, barium concentrations, and a bolus-hold swallowing paradigm, made comparisons to normative data impossible.

Our patients’ acuity further restricted our VFS assessments in many ways. First, we had to limit the number of boluses given during our VFS. While we recognize the physiological

differences that occur during swallowing when using cued rather than spontaneous swallowing

paradigms (Daniels, Schroeder, DeGeorge, Corey, & Rosenbek, 2007; Nagy et al., 2013), we had

to balance our chosen measurement methodologies that primarily utilize a bolus-hold with minimizing patient burden by limiting the number of bolus administrations. Second, all of our patients presented with either a central line or a nasogastric feeding tube. While we ensured the external portions of these radiographic artifacts were out of the image as much as possible, these items were likely a large contributor to our poor interrater reliability and will continue to pose challenges during the measurement processes in future acute-care studies. Finally, although the impact of nasogastric feeding tubes on swallowing is debatable (Huggins, Tuomi, & Young,

1999; Leder & Suiter, 2008; Wang, Wu, Chang, Hsiao, & Lien, 2006), we cannot determine what, if any, affect it had on the VFS measures.

While we were able to conduct VFSs successfully on consecutive patients shortly after extubation following CV surgery, the enrollment rate was such that it would not be feasible to conduct this study as presented on a larger scale. We were unable to successfully execute our study protocol with no patients agreeing to all procedures. The lessons learned throughout the process have assisted with study changes prior to future implementation. Future prospective

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studies should include patients intubated for 24 hours or more while allowing for instrumental

swallowing assessments throughout the week. Patient burden is minimized while using one

instrumental procedure and ideally, swallowing physiology should be documented using

standardized tools and objective physiological measurements in order to most reliably

characterize the swallow function of these patients. Due to the patient’s acuity, specifically

while in intensive care, FEES may be the most appropriate instrumental procedure. It can be

conducted at the bedside and is more conducive to: ruling out oropharyngeal and laryngeal

pathologies, serial examination allowing for documentation of swallowing recovery, and can be

expanded to include upper airway sensory testing. The benefits of using FEES however, must be

weighed against the limited interpretation tools currently available. The swallowing physiology

of recently extubated patients is so under-researched at this time, that it warrants investigation of all swallowing kinematics, temporal measures, and event sequences. As a result, VFS may be the instrumentation of choice if reporting physiology is the primary objective. Although dysphagia incidence and swallowing physiology of this population still remains elusive, our study provides the necessary foundation for successful conduct of future studies aiming to determine dysphagia frequency and characteristics in post-extubation patients.

DISCUSSION

CHAPTER V

DISCUSSION

Introduction

The series of three studies that comprise this dissertation make novel contributions to the dysphagia literature while focusing on the recently extubated as well as cardiovascular surgical patients. For our initial study, we were the first to conduct a systematic review of the literature focusing on endotracheal intubation and dysphagia (Skoretz, Flowers, et al., 2010). We ascertained that longer intubation durations are associated with higher dysphagia frequencies.

However, the evidence was limited by an overall paucity in the literature, poor study quality and a high risk of bias. Using this information, we designed and executed our two subsequent studies with sound methodology to minimize bias risk and characterize swallow physiology.

Specifically, our second study was the first to report dysphagia frequency according to stratified intubation durations after both coronary artery bypass and cardiac valve surgery (Skoretz et al.,

2014). We identified independent predictors of dysphagia while clarifying the intubation durations that posed the greatest risk for post-operative dysphagia. We used this intubation duration for our prospective and final study, aimed at assessing the feasibility and patient acceptance of instrumental swallowing assessments after CV surgery following prolonged intubation. We gathered feasibility data on several patient and study parameters. This study provided the first interpretation of videofluoroscopic swallow studies using standardized rating scales and kinematic measurements on consecutively enrolled patients following prolonged intubation after CV surgery. Although the recruitment was slow, proving our study was not feasible as designed, this study also provided numerous lessons regarding patient eligibility criteria, study impact on patient and nursing along with swallowing instrumentation and

137

DISCUSSION 138 interpretation methods. In sum, all three studies offer value to the clinical community and inform future studies. The findings from this research will provide the foundation for future large-scale prospective research that will properly validate the findings herein related to dysphagia incidence, swallowing physiology and identifying those with dysphagia after cardiovascular (CV) surgery following prolonged intubation.

Summary of Thesis Findings

Our systematic review was the first to evaluate all of the existing post-extubation dysphagia literature thereby providing an up-to-date summary of the evidence (Skoretz, Flowers, et al., 2010). Due to study heterogeneity in the existing literature, we were unable to conduct a meta-analysis and instead, provided a descriptive report of our findings. We confirmed that dysphagia incidence varies across diagnostic groups, ranging from three to 62% (de Larminat et al., 1995; Ferraris et al., 2001; Hogue et al., 1995; Rousou et al., 2000; Stanley et al., 1995), with no particular diagnosis associated with greater dysphagia risk. Regardless of etiology, the highest dysphagia frequencies occurred following prolonged intubation durations (Ajemian et al.,

2001; Barker et al., 2009; de Larminat et al., 1995).

As a whole, the available evidence espoused poor study quality and high risk of bias primarily due to study design. Many of the included studies were either retrospective observational studies (Barker et al., 2009; Ferraris et al., 2001; Padovani et al., 2008; Rousou et al., 2000) or failed to declare whether enrollment was consecutive (Burgess et al., 1979; Davis &

Cullen, 1974; de Larminat et al., 1995; Padovani et al., 2008; Stanley et al., 1995). In addition, there were many variations in study design particularly regarding the timing (Ajemian et al.,

2001; Barquist et al., 2001; Burgess et al., 1979; Davis & Cullen, 1974; de Larminat et al., 1995;

El Solh et al., 2003; Keeling et al., 2007; Leder, Cohn, et al., 1998) and type of swallowing

DISCUSSION 139 assessments (Ajemian et al., 2001; Barker et al., 2009; Barquist et al., 2001; Burgess et al., 1979;

Davis & Cullen, 1974; de Larminat et al., 1995; El Solh et al., 2003; Ferraris et al., 2001; Hogue et al., 1995; Keeling et al., 2007; Leder, Cohn, et al., 1998; Padovani et al., 2008; Rousou et al.,

2000; Stanley et al., 1995). These variations likely influenced the wide range of reported dysphagia frequencies and other study outcomes identified by our review.

Dysphagia assessment methods varied across included studies (Ajemian et al., 2001;

Barker et al., 2009; Barquist et al., 2001; Burgess et al., 1979; Davis & Cullen, 1974; de

Larminat et al., 1995; El Solh et al., 2003; Ferraris et al., 2001; Hogue et al., 1995; Keeling et al.,

2007; Leder, Cohn, et al., 1998; Padovani et al., 2008; Rousou et al., 2000; Stanley et al., 1995) with only one declaring blinding (Stanley et al., 1995). However, even in studies with similar assessment methods, dysphagia frequencies were inconsistent. Despite this, some general trends were noted. Specifically, those studies reporting the highest frequencies used FEES on all enrollees (Ajemian et al., 2001; El Solh et al., 2003). In contrast, the studies reporting the lowest dysphagia frequencies used debatably less sensitive methods to diagnose dysphagia including clinical assessments (Padovani et al., 2008) or static chest radiographs following the ingestion of radio-opaque contrast (Burgess et al., 1979; Davis & Cullen, 1974; Stanley et al., 1995). The majority of the included studies limited their outcome to aspiration (Ajemian et al., 2001;

Barquist et al., 2001; Burgess et al., 1979; Davis & Cullen, 1974; El Solh et al., 2003; Keeling et al., 2007; Leder, Cohn, et al., 1998; Stanley et al., 1995) with only a few declaring an operational definition for dysphagia (Barker et al., 2009; Barquist et al., 2001; El Solh et al., 2003; Leder,

Cohn, et al., 1998). Across all included studies, no psychometrically validated tools measuring both oral and pharyngeal function were utilized nor were any kinematic measurements

DISCUSSION 140

conducted. Additionally, none of the studies used validated tools for screenings, assessments, or

interpretation methods for all patients.

Our systematic review revealed other gaps in the literature, specifically with regards to

dysphagia research following CV surgery. With this population, most studies reported dysphagia frequency for cumulative intubation durations across the entire study sample (Ferraris et al.,

2001; Hogue et al., 1995; Rousou et al., 2000) or for durations greater than 48 hours (Barker et al., 2009). As a result, dysphagia frequencies for patients intubated for less than 48 hours for both coronary artery bypass grafting and valve surgery was essentially unknown.

Our second study was designed to address the noted deficiencies from our systematic review. Given that no previous study had targeted the relation between intubation duration and corresponding dysphagia frequencies, we incorporated this as our main objective (Skoretz et al.,

2014). Specifically, our second study assessed dysphagia frequencies according to the following intubation strata: ≤12.0 hours, >12.0 to ≤24.0 hours, >24.0 to ≤48 hours and greater than 48 hours. We were the first to document that dysphagia occurs most frequently in those intubated for greater than 48 hours when compared to lesser intubation times (Skoretz et al., 2014). Also, we were the first to confirm that dysphagia is in fact, negligible in patients intubated for ≤12 hours (Skoretz et al., 2014). Although, our dysphagia frequency across our entire sample was similar to previously published work (Ferraris et al., 2001; Hogue et al., 1995; Rousou et al.,

2000), we were the first to report that dysphagia frequencies exceed the cumulative population incidence for durations between 12 and 48 hours (Skoretz et al., 2014).

Not only did this study identify those at greatest risk of dysphagia relative to intubation duration, but we also identified independent predictors and associated risk factors for dysphagia in this population (Skoretz et al., 2014). We corroborated previous work reporting similar

DISCUSSION 141

independent predictors for dysphagia including: advanced age (Hogue et al., 1995), prolonged

intubation (Barker et al., 2009; Hogue et al., 1995) and sepsis (Barker et al., 2009). Our

findings, however, were the first to report that the odds of a patient having dysphagia increase by

a factor of two for every additional twelve hours of endotracheal intubation or for every

additional decade of age (Skoretz et al., 2014).

Prolonged intubation and thereby prolonged use of mechanical ventilation is precipitated by numerous factors following CV surgery (Reddy et al., 2007; Trouillet et al., 2009; Widyastuti et al., 2012; Yende & Wunderink, 2002). For example, those patients experiencing prolonged mechanical ventilation following CV surgery tend to be older (Cislaghi et al., 2009; Ji et al.,

2010; Légaré et al., 2001; Reddy et al., 2007; Suematsu et al., 2000) and more medically

complex (Cislaghi et al., 2009; Cohen et al., 2000; Combes et al., 2003; Pappalardo et al., 2004).

Barriers to early extubation often include impaired preoperative respiratory function (Ingersoll &

Grippi, 1991), multi-system inflammatory response (Ji et al., 2010; Widyastuti et al., 2012),

hemodynamic instability, bleeding, inadequate oxygenation (Doering, 1997), and acute

respiratory distress syndrome (Widyastuti et al., 2012). As a result, the duration for which

patients require mechanical ventilation is not typically dictated by a single variable therefore

intubation duration cannot truly be considered in isolation when exploring potential causative

factors for dysphagia. Rather intubation duration could be considered a measurable marker by

which clinicians may gauge dysphagia risk following extubation.

As already noted above and similar to previous research (Barker et al., 2009; Ferraris et

al., 2001; Hogue et al., 1995), our second study showed age as an independent predictor of

dysphagia in post-operative cardiovascular patients. Other work has shown that advanced age

results in more protracted recovery of swallowing following extubation when compared to

DISCUSSION 142

younger patients (El Solh et al., 2003). Unfortunately, no previous study has investigated

underlying physiological reasons for dysphagia and its poor recovery in elderly post-operative

CV patients.

In keeping with our goal to address gaps in the literature, our aim for our final study was to design and trial a small-scale study using prospective design and consecutive enrollment. In turn, this design may be utilized as a future large-scale study to then determine dysphagia

incidence and swallowing physiology of patients following CV surgery after prolonged

intubation. Therefore, our primary objective was to determine the feasibility and patient

tolerance of the instrumental procedures used to assess swallowing physiology in this population.

We assessed study impact on patient comfort, nursing workflow and each participant’s ability to

accommodate study procedures as well as other feasibility parameters including recruitment rate,

task completion durations and measurement reliability. The findings of our earlier studies

informed the design of this final study in the following areas: assessor blinding,

videofluoroscopy swallowing study (VFS) interpretation methods, and eligibility criteria the

intubation time point of > 48 hours for our study eligibility criteria. All enrolled patients were

able to participate in the VFS procedure making this work the first of its kind to describe

swallowing physiology on consecutively enrolled, recently extubated patients following CV

surgery using psychometrically validated and objective measures. In addition, all nursing staff

reported that our study had minimal impact on their workload.

In the end, however, our study as proposed proved not feasible. Specifically, our

recruitment was slow with no patients agreeing to all study assessments. We had poor patient

response rates to our study impact questionnaire and poor reliability of some VFS measures.

Even with these challenges, our study was successful as it provided the feasibility parameter

DISCUSSION 143 estimates we sought. These estimates will eventually inform future study designs and in doing so, improve enrollment and minimize patient burden. In addition, this study enabled us to reflect on the challenges of obtaining reliable VFS interpretations in this acutely ill patient population.

From this final study, several suggestions were derived for the future research with this population. Specifically, to increase enrollment we suggested the inclusion of: 1) multiple recruitment sites; 2) patients intubated for over 24 hours; and 3) access to instrumental swallowing assessments throughout the week. In addition, we suggested using only one rather than two instrumental procedures in order to minimize patient burden. However, which method to use depends on study objectives. If, for example, the primary objective is to report on physiology (Logemann, 1997; Logemann et al., 1998), swallowing kinematics along with timing measures of all oral, pharyngeal and upper airway structures (Kendall, McKenzie, Leonard,

Goncalves, & Walker, 2000; Leonard & McKenzie, 2006; Leonard et al., 2009; Leonard et al.,

2000; Steele et al., 2011), then the VFS would be the tool of choice. However, if the goal is to assess swallowing physiology by obtaining a direct view of the upper airway and therefore any structural problems, then FEES may be more appropriate (Hiss & Postma, 2003; Langmore,

2003; Langmore et al., 1988; Langmore et al., 1991).

FEES may in fact be the most ideal instrumentation for this patient population considering the likelihood that intubation poses high risk for upper aerodigestive tract pathologies (Langmore, 2003; Langmore et al., 1988). FEES ensures direct assessments of laryngopharyngeal pathologies (Hiss & Postma, 2003; Langmore, 2003; Langmore et al., 1988) while allowing for sensory testing (Aviv, 2000a; Aviv et al., 2000; Aviv, Kim, Sacco, et al.,

1998; Aviv, Kim, Thomson, et al., 1998) and serial examinations over time without excessive risks to patients (Hiss & Postma, 2003; Langmore, 2003; Langmore et al., 1988). Patients

DISCUSSION 144

undergoing CV surgery comprise a diagnostic group at increased risk of vocal fold immobility

(VFI) and its negative sequelae including airway penetration and aspiration (Bhattacharyya et al.,

2003; Itagaki et al., 2007; Joo et al., 2009).

Clinical Implications

Our collective findings have provided evidence to support clinical practice. From

dysphagia risk factors to the timing of oral intake following extubation, our contributions can be

utilized in the identification of patients at risk for dysphagia. Our findings have underscored the

need for focused clinical observation and speech-language pathology service provision

particularly for those patients who are elderly, medically complex or intubated for periods of

greater than 24 hours.

Across our studies we have shown that dysphagia is indeed prevalent in the days

following extubation particularly following prolonged intubation (Skoretz, Flowers, et al., 2010;

Skoretz et al., 2014). In our systematic review, the studies reporting the highest dysphagia

frequencies conducted assessments within 48 hours of extubation regardless of patient diagnosis

(Skoretz, Flowers, et al., 2010). In our second study, we ensured our identification of dysphagia

was in close time proximity to extubation proving that following extubation, particularly

following intubation periods of greater than 24 hours, dysphagia occurs in nearly one of every

two patients (Skoretz et al., 2014). Furthermore, in our final prospective feasibility study, we

observed that pharyngeal swallowing impairments persist for at least 48 hours following extubation. As a result, patients who were intubated for greater than 24 hours should be closely monitored when oral feeding is initiated following extubation.

Not only has our research highlighted the need for attending medical staff to monitor the swallow function of those at-risk patients following extubation, but our collective findings may

DISCUSSION 145

also be used to inform clinical guidelines and advocate for qualified dysphagia personnel. From

our work we have determined a dysphagia risk profile for this patient population. Those patients

at greatest risk of dysphagia following CV surgery have been intubated for greater than 24 hours,

are 70 years of age or older and have post-operative sepsis. Early dysphagia diagnosis and intervention minimizes morbidities and shortens the duration of hospitalizations (Altman et al.,

2010). At the time of this writing, stroke is the only diagnoses for which published guidelines have been established for dysphagia assessment and management (Jauch et al., 2013; Lindsay et al., 2008). Recommended practice suggests that swallowing screenings, and upon screening failure, swallowing evaluations be conducted on stroke patients early upon admission and prior to the initiation of oral intake of food or fluids (Casaubon, Suddes, & Acute Stroke Best

Practices Working Group 2013, 2013). Our findings have provided evidence enabling the construction of a risk profile for recently extubated post-operative CV patients. As a result, we suggest that similar guidelines be developed with the inclusion of our risk factors in order to ensure high-quality provision of care and positive patient outcomes.

Collectively, the findings from our three studies confirm high dysphagia risk for patients following extubation, and with the risk factors of prolonged intubation, advance age and medical complexity identified in our first and second studies, we have provided the items needed for a cardiac dysphagia risk index. This tool, when used in conjunction with a validated bedside swallowing screening assessment, would help attending medical staff in the identification of “at- risk” patients soon after extubation following CV surgery. Ultimately, these collective steps would enable early dysphagia diagnosis and management, reduce possible complications secondary to dysphagia and as a result, improve patient outcomes and minimize healthcare costs.

DISCUSSION 146

Research Implications

At present, there are no validated tools by which to identify patients who are at risk for

dysphagia following CV surgery. With the findings of our current work providing the

information needed for a cardiac dysphagia risk index and, along with the lessons learned from

our feasibility study, we have the foundation necessary to inform aspects of a validation study for

this risk index. Moving forward, this future work would be done in two stages. First, we would

determine if other factors, particularly operative variables, should be considered for inclusion in

our risk index. Second, using the findings of this first stage and the outcomes of our feasibility

study, we would propose a validation study, which would determine if our index could identify

cardiac patients at risk for dysphagia.

Along with the independent predictors identified in our current work, which include age

and intubation duration, special consideration should be given to other factors significantly

associated with dysphagia, particularly operative variables, in the development of this cardiac

dysphagia risk index. While not independent predictors, we reported in our second study that

more patients with dysphagia underwent valve surgery, required peri-operative TEE and had

longer cardiopulmonary bypass times (Skoretz et al., 2014). Those with dysphagia also required inotropic support and intra-aortic balloon pump placement more frequently (Skoretz et al., 2014).

These dysphagia risk factors, specifically surgery type (Barker et al., 2009; Ferraris et al., 2001),

peri-operative TEE (Hogue et al., 1995; Rousou et al., 2000) and intra-aortic balloon pump placement (Hogue et al., 1995) corroborate the findings of previous studies. Furthermore, although debatable (Sellke et al., 2005), particular cardiac interventions have been associated with other adverse short-, mid- and/or long-term outcomes as well (Ivanov et al., 2008; Moller,

Penninga, Wetterslev, Steinbruchel, & Gluud, 2008; van Dijk et al., 2000; Wijeysundera et al.,

DISCUSSION 147

2005). For example, patients undergoing valve surgery, particularly when involving multiple cardiac interventions, are at increased risk of post-operative morbidities including stroke (Ricotta et al., 1995; Vasques, Lucenteforte, et al., 2012) and gastrointestinal complications (Bolcal et al.,

2005; D'Ancona et al., 2003). Additionally, prolonged cardiopulmonary bypass, aortic cannulation and cross clamping durations have been implicated in the precipitation of adverse outcomes (Nissinen et al., 2009).

When considered together, both in our research and others, variables including surgery type (Barker et al., 2009; Ferraris et al., 2001; Skoretz, Flowers, et al., 2010), peri-operative TEE

(Hogue et al., 1995; Rousou et al., 2000; Skoretz, Flowers, et al., 2010; Skoretz et al., 2014) and intra-aortic balloon pump placement (Hogue et al., 1995; Skoretz, Flowers, et al., 2010; Skoretz et al., 2014) may indicate more severe disease and/or greater surgical complexity therefore increasing the patient’s risk for complications including dysphagia. However, without an objective measure for surgical complexity or studies comparing specific cardiac interventions or operative variables and their subsequent swallowing outcomes, the usefulness of surgery type or operative variables in the risk index is only speculative. Future work should compare swallowing outcomes across surgery types, including isolated, multiple or combination surgeries for valve and/or bypass along with the inclusion of minimally invasive approaches using a consecutive patient sample large enough to allow for detailed comparisons.

Once the complete index is derived, the next step would be to conduct a validation study in order to determine if our index is able to identify patients at risk of dysphagia. The validation of our cardiac dysphagia risk index would ultimately involve a consecutive sample of post- surgical CV patients from multiple institutions following intubation periods of 24 hours or longer using prospective enrollment. In order to reliably identify the presence of post-extubation

DISCUSSION 148

dysphagia, all patients would undergo and instrumental swallowing assessment within 48 hours

following extubation.

Future Studies

While our line of research provided novel contributions to the literature and clinically applicable findings, many questions remain unanswered regarding post-extubation dysphagia.

Ultimately, future research goals should enable clinicians to identify patients who are at greater risk of dysphagia enabling them to target appropriate interventions. In order to do so, future research endeavours should include homogeneous patient populations or larger sample sizes and rigorous methodology. Answering the question of “who is at risk for post-operative dysphagia” whole or in part, requires further investigation of swallowing physiology including upper airway, anesthesia and respiratory variables in order to systematically target measurable dysphagia risk factors in recently extubated patients.

The ultimate goal of our line of research was to design a future large-scale protocol that would provide the most objective and comprehensive measurement of post-extubation swallowing physiology. Moving forward from this work, our goal is to conduct a study using comprehensive swallowing measures on patients following prolonged intubation after CV surgery in order to document the swallowing physiology of this population. If using videofluoroscopy, we would include structural displacement, timing and latency measurements across all swallowing stages along with measures of structural movement, airway penetration, aspiration and residue using psychometrically validated scales. Future assessment protocols should also incorporate previously published barium concentrations, bolus size and textures, swallowing paradigms and bolus administration techniques in order to allow for comparisons to other work.

DISCUSSION 149

Our motivation to include nasendoscopy in our third study was to provide the foundation

for determining the impact of laryngopharyngeal morbidity and upper airway sensitivity on

swallowing physiology, particularly airway protection capabilities, in recently extubated patients

following CV surgery. The inclusion of FEESST into future work would not only provide

objective information regarding swallowing physiology (Aviv, 2000a; Aviv et al., 2000; Aviv,

Kim, Sacco, et al., 1998; Aviv, Kim, Thomson, et al., 1998), it would also provide further

diagnostic information regarding those at risk for post-extubation dysphagia and whether the inclusion of upper airway related information, such as endotracheal tube size or induction medications, should be included in a cardiac dysphagia risk index.

Intubation has been deemed a potential antagonist of swallowing physiology and airway protection (Postma et al., 2007; Tolep et al., 1996). In addition, those patients with cardiac pathologies (Adkins et al., 1986; Cappell, 1991, 1995; Dines & Anderson, 1966) or those undergoing CV surgery (Itagaki et al., 2007; Joo et al., 2009; Rosenthal et al., 2007) comprise

diagnostic groups at increased risk of vocal fold immobility. While many studies have reported

on upper airway pathologies following extubation (Colice et al., 1989; Colton House et al., 2011;

Mencke et al., 2003; Owall et al., 1992; Santos et al., 1994; Stauffer et al., 1981; Tadié et al.,

2010; Thomas et al., 1995; Wittekamp, van Mook, Tjan, Zwaveling, & Bergmans, 2009) or

alternatively, have suggested a link between swallowing impairment and these pathologies

(Postma et al., 2007; Tolep et al., 1996), no study has systematically investigated this dynamic specifically following recent extubation. Presently, no study has determined airway sensory thresholds, and thereby glottal competence, and its relationship to swallowing physiology of recently extubated patients of varying intubation durations. As a result, incorporating the use of

FEESST would begin the process of cataloguing upper airway sensory thresholds (Aviv, 2000a;

DISCUSSION 150

Aviv et al., 2000; Aviv, Kim, Sacco, et al., 1998; Aviv, Kim, Thomson, et al., 1998) while linking these thresholds to airway protection mechanisms in this population.

Post-extubation respiratory variables, including respiration rate and lung volumes, may prove to be informative in the determination of dysphagia risk following extubation. The respiration of patients with medical diagnoses such as stroke (Leslie, Drinnan, Ford, & Wilson,

2002) or chronic obstructive pulmonary disease (Gross et al., 2009; Mokhlesi, Logemann,

Rademaker, Stangl, & Corbridge, 2002) or of those following recent extubation (Hasegawa &

Nishino, 1999; Jian, Sheng, Min, & Zhongxiang, 2013; Nishino, 2012; Nishino et al., 1998;

Nishino & Hiraga, 1991), often differs from that of healthy individuals (Krieger et al., 1988).

Alterations in respiratory cycling (Gross et al., 2009; Hasegawa & Nishino, 1999; Nishino, 2012;

Nishino et al., 1998; Nishino & Hiraga, 1991), lung volumes (Gross et al., 2003; Mokhlesi et al.,

2002), swallow apneic periodicity (Hasegawa & Nishino, 1999; Nishino, 2012; Nishino et al.,

1998; Nishino et al., 1989) and respiratory rate (Hasegawa & Nishino, 1999; Leslie et al., 2002;

Nishino, 2012; Nishino et al., 1998; Nishino et al., 1989) can induce changes in swallowing physiology increasing the individual’s risk of prandial aspiration. While these respiratory variations and their impact on swallowing have been documented for numerous diagnostic groups (Gross et al., 2009; Leslie et al., 2002; Mokhlesi et al., 2002; Nishino & Hiraga, 1991) along with healthy subjects (Gross et al., 2003; Isono et al., 1991; Nishino et al., 1998; Nishino et al., 1989; Nishino, Takizawa, Yokokawa, & Hiraga, 1987), these details are lacking in those who have been recently extubated. Future studies should compare pre- and post-intubation swallowing and respiratory measurements thereby determining whether the risk or severity of dysphagia increases as a result of respiratory factors.

DISCUSSION 151

Limitation of the Thesis

Throughout our systematic review, we espoused stringent selection criteria, blinding and excluded known causes of dysphagia. Despite this rigor, we were limited by the existing literature given the heterogeneity and bias risk across included studies. Few studies have been published on post-extubation dysphagia and those that met our inclusion criteria, had heterogeneous patient samples and when compared to each other, varied in regards to their identification of dysphagia. Given this heterogeneity across numerous design aspects, a meta-

analysis was impossible. As a result, we were unable to: 1) determine effect of intubation

duration on the frequency of dysphagia across all studies and 2) calculate the relative risk of

dysphagia following a range of intubation durations. Instead, we were able to report dysphagia

frequencies according to diagnostic group, provide a comprehensive review of dysphagia- associated risk factors and evaluate the quality of the existing literature.

Our second study was limited by virtue of its retrospective design. While we utilized blinding throughout our chart reviews and were conservative in our identification of dysphagia, identifying dysphagia retrospectively presents limitations. Since very few patients had received instrumental swallowing assessments, we had to rely upon clinical speech-language pathology assessments as well as surrogate nutrition variables such as modified texture diets or tube feeding. In addition, we were unable to investigate variables that may potentially affect postoperative swallowing physiology such as baseline swallowing status, medical conditions that may predispose a patient to dysphagia as well as post-operative delirium. Finally, our data was collected at a single large, quaternary care cardiac center serving a multi-cultural urban center.

While our results may potentially be applicable to similar institutions, the generalizability of our findings is yet unknown.

DISCUSSION 152

Our final study was designed and executed as a feasibility study. By definition, it was

descriptive and exploratory in nature. Despite this, we ensured methodological rigor throughout

the process including a study protocol determined a priori, consecutive prospective enrollment and assessor blinding. Due to the limited number of patients enrolled, we were unable to conduct statistical comparisons of our swallowing outcomes and as a result, the swallowing physiology we described is unlikely to be representative of the population as a whole. The acuity of our patients also restricted VFS duration, conduct and interpretation. For example, we were able to administer only a limited number of oral trials and due to patient mobility restrictions, we conducted lateral fluoroscopic views only. Additionally, all of our patients had a nasogastric tube and/or central line present during the VFS and in our field of view. While we attempted to adjust the lines to the best of our ability, these were likely factors in the poor reliability of some VFS measures. We included nasendoscopy in our protocol due to the likelihood of upper airway pathologies in a population such as this. Unfortunately, no patient agreed to the procedure thereby limiting our ability to assess the possible impact of upper airway pathologies on swallow physiology. Regardless of the limitations throughout each of our studies, we were able to ensure that our study definitions and protocols were determined a priori,

our studies utilized consecutive enrollment, and that our reviewers and/or assessors were blinded

to each other and clinical data as applicable.

Conclusions

We have made novel contributions to the post-extubation dysphagia literature, which

have implications for clinical practice and research. With the completion of our studies, we were

the first to: evaluate the post-extubation dysphagia literature, confirm the high frequency of

DISCUSSION 153

dysphagia following extubation regardless of diagnosis, and report on the association between

intubation duration and dysphagia following CV surgery.

Throughout our systematic review, we were the first to confirm that prolonged intubation

durations are associated with higher dysphagia risk regardless of diagnosis. We also determined

that identified studies were inherently limited by their design and as a result, are of very low

quality with high risk of bias. There are relatively few studies with specific outcomes focusing

on dysphagia following intubation and even fewer focusing on swallowing physiology following

CV surgery.

Given the need for further research on post-extubation dysphagia while using homogeneous patient populations and rigorous methodology, our second study included only consecutive patients following CV surgery. We were the first to stratify dysphagia frequencies according to clinically meaningful intubation durations and subsequently demonstrated that those with the highest risk of dysphagia following CV surgery experience intubation periods greater than 48 hours. We identified numerous risk factors associated with dysphagia as well as independent predictors including age, sepsis and prolonged intubation. Collectively, these findings may assist clinicians in gauging a patient’s dysphagia risk through the use of these measurable surrogate variables.

While our final study proved not feasible as designed, it was an important first step in determining the most suitable instrumental and interpretation methods for assessing swallowing physiology following prolonged intubation after CV surgery. This study afforded us the opportunity to evaluate the study design, execution and patient tolerance of diagnostic tests used to evaluate post-operative swallow function. We were the first to conduct displacement and

DISCUSSION 154

physiological measurements using psychometrically validated tools on these patients.

Furthermore, we determined that the impact of our research was minimal on study participants.

Future prospective studies are needed to elucidate both risk factors and swallowing

physiology of recently extubated patients. In order to develop tools to identify at-risk patients,

we need to determine the impact of other perioperative or comorbid factors on the swallow as

well as those that affect dysphagia severity and/or recovery. While the prospective incidence of dysphagia as well as the swallowing physiology of CV surgical patients remains elusive, our line of research has provided the foundation for the successful conduct of future studies focusing on the mechanisms underlying dysphagia in these recently extubated patients. We have confirmed that this diagnostic sub-group is one at greater risk of dysphagia and provided risk factors that

may be used to identify these patients. Ultimately, our findings will inform clinical practice and

as a result, improve patient outcomes.

REFERENCES 155

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APPENDICES 225

Appendix A – CHEST Licenses

APPENDICES 226

APPENDICES 227

APPENDICES 228

APPENDICES 229

APPENDICES 230

APPENDICES 231

APPENDICES 232

APPENDICES 233

APPENDICES 234

APPENDICES 235

APPENDICES 236

APPENDICES 237

Appendix B - Systematic Review Proposal

The Question Is duration of intubation associated with the outcome of dysphagia in adults?

Operational Definitions Intubation – the presence of an endotracheal tube in the oropharynx

Duration – time length: may be specified in minutes, hours or days

Dysphagia – is defined as any impairment or abnormality of the oral, pharyngeal or upper esophageal stage of deglutition. Dysphagia, or deglutition disorders, may be identified by clinical swallow evaluations (CSE) or instrumental assessment techniques which include, but are not limited to, videofluoroscopic swallow study (VFSS) or fiberoptic endoscopic evaluation of the swallow (FEES)

Inclusion and Exclusion Criteria Inclusion: Participants – Adults (>18 years) who have undergone endotracheal intubation during their hospitalization Assessment Methods/Outcomes – Studies reporting the presence or absence of dysphagia as assessed/reported through clinical swallow evaluations or instrumental assessment techniques (including but not limited to VFSS or FEES) Study designs - Case series (n>10), retrospective or prospective descriptive studies with consecutive enrollment, and case control studies

Exclusion: Participants- Studies with samples including pediatric enrollees will be excluded unless they comprise <25% of the study’s total sample. Those studies including patients with tracheostomy tubes will be excluded unless: they comprise <25% of the study’s total sample, study authors included individual patient data or some statistical analyses excluded those with tracheostomy tubes. Assessment Methods/Outcomes – Studies using patient report to describe dysphagic symptoms will be excluded. Studies focusing on dysphagia secondary to distal esophageal or gastric etiologies will also be excluded. Studies that fail to compare patients without dysphagia to those with dysphagia on the variables of interest will also be excluded. Study designs – Case series (n<10)

APPENDICES 238

Data Sources A. Database search strategies. 1) Searches using “deglutition”, “deglutition disorders”, “dysphagia” and “intubation” (see reviewer’s terms attached)

2) Databases: • MEDLINE (Ovid) 1950-current • EMBASE (Ovid) 1980-current • CINAHL (Ovid) 1982-current • PsycINFO (Ovid) 1960-current • AMED (Ovid) 1985-current • HealthSTAR (Ovid) • BIOSIS Previews 1980-current

B. Manual searching. Manual searches of the following journals will be conducted using keywords of “swallowing”, “swallowing disorders”, “deglutition disorders”, “dysphagia” and “intubation” for the years 1988 to present. Manual searching will be conducted online for those years that are available. 1) Annals of Thoracic Surgery 2) The Journal of Thoracic and Cardiovascular Surgery 3) Critical Care Medicine 4) American Journal of Roentgeneology 5) Intensive Care Medicine 6) Chest 7) Journal of Anesthesia 8) The American Journal of Cardiology 9) Archives of Surgery 10) Heart and Lung Journal of Acute and Critical Care 11) Dysphagia 12) Canadian Journal of Surgery 13) Anaesthesia 14) Radiology 15) Radiographics 16) Circulation

C. Conference proceedings. 1) American Society of Anesthesiologists 2) UK Swallowing Research Group (2005-current) 3) European Study Group for Dysphagia and Globus The following conference proceedings will be captured during manual searching of their respective journals (in brackets): 1) Dysphagia Research Society (Dysphagia) 2) American Heart Association scientific sessions (Circulation) 3) Radiological Society of North America scientific sessions (Radiology)

APPENDICES 239

D. Unpublished sources. 1) Doctoral dissertations as indexed on ProQuest Dissertations and Theses 2) Personal communication with known authors 3) Grey literature • GrayLIT network accessed by http://www.science.gov • Grey Source accessed by http://www.greynet.org/greycourse.index.html • OpenSigle accessed by http://www.utoronto.ca

E. Cited references and reference lists from selected articles

Study Selection Two observers, blinded to each other, will assess eligibility of each study. Disagreement will be resolved by consensus.

Risk of Bias Assessment and Assessment of Study Quality Included studies will be assessed using the Risk of Bias Assessment tool and adapted GRADE approach as recommended by the Cochrane Collaboration (Higgins et al., 2008).

Data Extraction Two independent observers will extract data from the selected studies. They will be blinded to each other’s results. Where available, the outcome of dysphagia, its operational definition, method of assessment, and specific dysphagia findings will be captured. Where available, variables pertaining to specific patient groups including duration of intubation and patient characteristics will be captured. Where available, consequences of dysphagia will also be extracted.

Analyses and Presentation of Results The results will be summarized descriptively and using the tables and figures as recommended by the Cochrane Collaboration (Higgins et al., 2008). Summary of Findings tables with adapted headings will be used. Results will likely reveal high risk of bias along with poor study quality. Where possible meta-analyses will be conducted (e.g. relative risk calculations).

APPENDICES 240

Appendix C – Study Selection Form

Yes/Unknown No Appropriate study type? [Reject case studies n<10, tutorial or educational papers] Adult patient group in study? [Reject if adult patients<10] Any oropharyngeal and upper esophageal dysphagia outcomes reported? [Reject if outcomes reported only during intubation] [Reject if only mid and lower esophageal outcomes] Patients underwent endotracheal intubation? [Reject if intubated patients <10] [Reject if patients intubated via endoscopy for stent placement (e.g., Atkinson/Celestin tubes), pulsion technique, laser technique] [Reject if noninvasive intubation techniques used]

Note: Some etiologies (e.g., diagnosis of stroke) or operative procedures (e.g. general anesthetic & surgical intervention for malignant dysphagia) may have required patient to undergo endotracheal intubation during a hospitalization [Reject only if explicitly reported that the patients were NOT intubated]

All inclusion criterion met (circle one): YES NO

APPENDICES 241 Appendix D – Cochrane Collaboration’s Risk of Bias Assessment Tool

Domain Description Review authors’ judgment Sequence generation Was the allocation sequence adequately generated?

YES / NO / UNCLEAR

Allocation concealment Was allocation adequately concealed?

YES / NO / UNCLEAR

Blinding of participants, Was knowledge of the allocated intervention personnel and outcome adequately prevented during the study? assessors Outcome: YES / NO / UNCLEAR

Incomplete outcome data Were incomplete outcome data adequately Outcome: addressed?

YES / NO / UNCLEAR Incomplete outcome data Were incomplete outcome data adequately Outcome: addressed?

YES / NO / UNCLEAR

Selective outcome reporting Are reports of the study free of suggestion of selective outcome reporting?

YES / NO / UNCLEAR

Other sources of bias Was the study apparently free of other problems that could put it at a high risk of bias?

YES / NO / UNCLEAR

APPENDICES 242 Appendix E – Data Extraction Form

Study Patient Sample Dysphagia Assessment Intubation Data Study Outcome Author/Year Design Diagnoses Included for Enrollment Age Incidence Method Timing Follow-up Duration Prolonged Findings/Risk (N) review (n) Criteria (range/mean) (Mean) Definition Factors

APPENDICES 243

Appendix F – Exploratory Meta-Analyses

Methods

Post-hoc meta-analyses were conducted using studies that reported on the following

duration variables: intubation duration, hospital length of stay and intensive care unit (ICU)

length of stay. The weighted mean differences of each duration variable were compared

according to those with and without dysphagia using random effects statistical modeling.

Random effects model was employed in order to minimize the effect of within and between

study variance (Borenstein, 2009; Higgins, Whitehead, & Simmonds, 2011). Heterogeneity was analyzed using the T2 and the I2 statistics. T2 reflects the dispersion or actual variance while the

I2 reports the proportion of variance between studies (Borenstein, 2009; Higgins & Thompson,

2002; Higgins et al., 2011). I2 cutpoints of 25%, 50% and 75% were considered low, moderate

and high heterogeneity respectively (Higgins et al., 2008). Meta-analyses were conducted using the Cochrane Collaboration software program Review Manager (RevMan, version 5.0.20; The

Nordic Cochrane Centre; Copenhagen, Denmark). These exploratory findings were not included in the published manuscript.

Results

Six studies reported on intubation duration (Barker et al., 2009; Barquist et al., 2001; El

Solh et al., 2003; Hogue et al., 1995; Leder, Cohn, et al., 1998; Rousou et al., 2000), four reported on hospital length of stay (Barker et al., 2009; Ferraris et al., 2001; Hogue et al., 1995;

Rousou et al., 2000) and two reported ICU length of stay (El Solh et al., 2003; Hogue et al.,

1995). When comparing those with and without dysphagia, the summary estimates of intubation duration (Figure F.1.), hospital length of stay (Figure F.2.) and ICU length of stay (Figure F.3.)

APPENDICES 244

were: 77.18h (95% CI 33.51-120.84), 17.15h (95% CI 11.19-23.0) and 6.33h (95% CI 1.37-

11.29) respectively. The heterogeneity statistics are summarized in Table F.1.

Table F.1.

Heterogeneity statistics

Statistic Variable 2 2 T I (%)

Intubation duration 2127.6 90.0

Hospital LOS 41.9 95.0

ICU LOS 17.4 94.0

Note. LOS = length of stay; ICU = intensive care unit.

Discussion

In our original publication of this systematic review, we reported that with increasing

intubation durations, we found an increase in the frequency of dysphagia; however, due to the

heterogeneity of patient diagnoses, study methodology and outcomes across accepted studies, we

summarized all results descriptively. This exploratory meta-analysis supported our descriptive findings statistically in the following ways: 1) summary estimates revealed that longer weighted mean durations of intubation, hospitalization and ICU stay favoured an increased frequency of dysphagia and 2) high statistical heterogeneity was determined both within and across studies.

When comparing the forest plots across all duration variables, all studies reporting on hospital length of stay (Barker et al., 2009; Ferraris et al., 2001; Hogue et al., 1995; Rousou et al., 2000) favoured increased frequency of dysphagia with longer durations while reporting the highest degrees of precision, as evidenced by the smallest confidence intervals. In contrast when

APPENDICES 245 comparing studies reporting on intubation duration, one study (Barquist et al., 2001) favoured shorter intubation durations with higher frequencies of dysphagia while the remaining studies reported the opposite (Barker et al., 2009; El Solh et al., 2003; Hogue et al., 1995; Leder, Cohn, et al., 1998; Rousou et al., 2000). This comparison also revealed the largest confidence intervals most notably in studies with the smallest sample sizes (Barquist et al., 2001; El Solh et al., 2003;

Leder, Cohn, et al., 1998).

When tested statistically, all included studies had high degrees of heterogeneity. Both the

T2 and I2 statistics reveal marked heterogeneity with high dispersion and variance proportions across and between all studies (Barker et al., 2009; Barquist et al., 2001; El Solh et al., 2003;

Ferraris et al., 2001; Hogue et al., 1995; Leder, Cohn, et al., 1998; Rousou et al., 2000).

In conclusion, this meta-analysis, albeit exploratory, confirms our descriptive findings.

While the findings are not surprising considering the collinear nature of the duration variables, longer durations of intubation, and thereby longer lengths of stay in the intensive care unit and hospital, are associated with higher frequencies of dysphagia. These findings support our call for large, high quality studies in this area using homogeneous patient samples.

Dysphagia No dysphagia Mean Difference Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI Barker et al., 2009 142.4 63 130 87.1 43.3 124 22.8% 55.30 [42.06, 68.54] Barquist et al., 2001 254.4 175.2 7 288 235.2 63 6.7% -33.60 [-175.79, 108.59] El Sohl et al. 2003 187.2 165.6 22 148.8 127.2 20 11.9% 38.40 [-50.46, 127.26] El Sohl et al. 2003 223.2 156 15 184.8 112.8 27 11.8% 38.40 [-51.28, 128.08] Hogue et al., 1995 124.8 40.8 28 50.4 4.8 816 22.7% 74.40 [59.28, 89.52] Leder et al., 1998 346.56 298.56 9 283.68 192 11 3.2% 62.88 [-162.78, 288.54] Rousou et al., 2000 200.9 75 23 15.3 1.6 815 20.9% 185.60 [154.95, 216.25]

Total (95% CI) 234 1876 100.0% 77.18 [33.51, 120.84] Heterogeneity: Tau² = 2127.57; Chi² = 62.02, df = 6 (P < 0.00001); I² = 90% -200 -100 0 100 200 Test for overall effect: Z = 3.46 (P = 0.0005) Shorter durations Longer durations

Figure F.1. Weighted mean difference of intubation duration according to those with and without dysphagia.

APPENDICES 246

Dysphagia No dysphagia Mean Difference Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI Barker et al., 2009 26.1 15.6 130 16.2 11 124 19.9% 9.90 [6.59, 13.21] Ferraris et al., 2001 16.1 11.7 31 5.7 3.1 1011 19.3% 10.40 [6.28, 14.52] Hogue et al., 1995 33.4 4.4 28 12.3 0.4 816 20.9% 21.10 [19.47, 22.73] Rousou et al., 2000 34.5 5 13 7.9 0.4 699 20.4% 26.60 [23.88, 29.32] Rousou et al., 2000 28.1 6.2 10 11 1 116 19.5% 17.10 [13.25, 20.95]

Total (95% CI) 212 2766 100.0% 17.15 [11.29, 23.00] Heterogeneity: Tau² = 41.88; Chi² = 82.48, df = 4 (P < 0.00001); I² = 95% -100 -50 0 50 100 Test for overall effect: Z = 5.74 (P < 0.00001) Shorter LOS duration Longer LOS duration

Figure F.2. Weighted mean difference of hospital LOS according to those with and without dysphagia.

Dysphagia No dysphagia Mean Difference Mean Difference Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI El Sohl et al. 2003 14.4 3.3 22 9.4 3.3 20 34.8% 5.00 [3.00, 7.00] El Sohl et al. 2003 13.4 7.3 15 10.9 5.3 27 29.1% 2.50 [-1.70, 6.70] Hogue et al., 1995 15.1 3.1 28 4.4 0.2 816 36.1% 10.70 [9.55, 11.85]

Total (95% CI) 65 863 100.0% 6.33 [1.37, 11.29] Heterogeneity: Tau² = 17.39; Chi² = 32.99, df = 2 (P < 0.00001); I² = 94% -100 -50 0 50 100 Test for overall effect: Z = 2.50 (P = 0.01) Shorter LOS duration Longer LOS duration

Figure F.3. Weighted mean difference of ICU LOS according to those with and without dysphagia.

APPENDICES 247

Appendix G - Search Strategies Across Databases.

Databases Search strategya Yieldb AMED [(SH “Deglutition Disorders” exp) OR (“dysphagia.mp” OR “deglutition disorder*.mp” OR “swallow*.mp”) OR (swallow: adj2 15 ref dysfunction:).mp OR (swallow: adj2 deficit:).mp OR (impair: adj3 swallow:).mp OR (swallow: adj2 disturb:).mp OR (swallow: adj2 disorder:).mp OR (swallow: adj2 difficult:).mp] OR (swallow: adj2 abnormal:).mp OR (swallow: adj2 problem:).mp] AND [(SH “Intubation” exp) OR (“intubat*.mp”)] BIOSIS Previews (TS “dysphagia”, OR TS “deglutition disorder*”, OR TS “swallow*”, OR TS “intubat*”) AND (TN = Humans) 265 ref CINAHLc [(SH “Deglutition Disorders” exp) OR (“dysphagia.mp” OR “deglutition disorder*.mp” OR “swallow*.mp”) OR (swallow: adj2 71 ref dysfunction:).mp OR (swallow: adj2 deficit:).mp OR (impair: adj3 swallow:).mp OR (swallow: adj2 disturb:).mp OR (swallow: adj2 disorder:).mp OR (swallow: adj2 difficult:).mp] OR (swallow: adj2 abnormal:).mp OR (swallow: adj2 problem:).mp] AND [(SH “Intubation” OR SH “Intratracheal intubation” OR SH “Laryngeal masks”) OR (“intubation.mp” OR “intubat*.mp”)] CINAHLd [(MH “Deglutition Disorders” exp) OR (TX “dysphagia” OR TX “deglutition disorder*” OR TX “swallow*”) OR (TX swallow* N2 90 ref dysfunction*) OR (TX swallow* N2 deficit*) OR (TX impair* N3 swallow*) OR (TX swallow* N2 disturb*) OR (TX swallow* N2 disorder*) OR (TX swallow* N2 difficult*) OR (TX swallow* N2 dysfunction*) OR (TX swallow* N2 problem*) OR (TX swallow* N2 abnormal*)] AND [(MH “Intubation” OR MH “Intratracheal intubation” OR MH “Laryngeal masks”) OR (TX “intubat*”)] EBM Reviewse (“deglutition disorder*.mp” OR “dysphagia.mp” OR “swallow*.mp” OR “swallowing disorder*.mp”) AND (“intubat*.mp”) 113 ref EMBASE [(SH “Dysphagia” exp) OR (“dysphagia.mp” OR “deglutition disorder*.mp” OR “swallow*.mp” OR (swallow: adj2 dysfunction:).mp OR 606 ref (swallow: adj2 deficit:).mp OR (impair: adj3 swallow:).mp OR (swallow: adj2 disturb:).mp OR (swallow: adj2 disorder:).mp OR (swallow: adj2 difficult:).mp] OR (swallow: adj2 abnormal:).mp OR (swallow: adj2 problem:).mp] AND [(SH “Endotracheal intubation” OR SH “Nasotracheal intubation” OR SH “Intubation” OR SH “Respiratory tract intubation”) OR (“intubation.mp” OR “intubat*.mp”)] Healthstar [(SH “Deglutition Disorders” exp) OR (“dysphagia.mp” OR “deglutition disorder*.mp” OR “swallow*.mp”) OR (swallow: adj2 588 ref dysfunction:).mp OR (swallow: adj2 deficit:).mp OR (impair: adj3 swallow:).mp OR (swallow: adj2 disturb:).mp OR (swallow: adj2 disorder:).mp OR (swallow: adj2 difficult:).mp] OR (swallow: adj2 abnormal:).mp OR (swallow: adj2 problem:).mp] AND [(SH “Intubation” OR SH “Intratracheal intubation” OR SH “Laryngeal masks”) OR (“intubation.mp” OR “intubat*.mp”)] Medline [(SH “Deglutition Disorders” exp) OR (“dysphagia.mp” OR “deglutition disorder*.mp” OR “swallow*.mp”) OR (swallow: adj2 767 ref dysfunction:).mp OR (swallow: adj2 deficit:).mp OR (impair: adj3 swallow:).mp OR (swallow: adj2 disturb:).mp OR (swallow: adj2 disorder:).mp OR (swallow: adj2 difficult:).mp] OR (swallow: adj2 abnormal:).mp OR (swallow: adj2 problem:).mp] AND [(SH “Intubation” OR SH “Intratracheal intubation” OR SH “Laryngeal masks”) OR (“intubation.mp” OR “intubat*.mp”)] PsycInfo [(DE “dysphagia” OR DE “deglutition disorder*”) OR “swallow*”, OR “dysphagia” OR “pharyngeal disorder”] AND (“intubat*”) 29 ref

Note. AMED = Allied and Complementary Medicine; SH = subject heading (MeSH in Medline and Healthstar); exp = explode heading term; .mp = multi-purpose field location; adjn = defined adjacency (Ovid platform); TS = subject terms; TN = taxa notes; ref = references; CINAHL = Cumulative Index of Nursing and Allied Health; MH = major heading; Nn = defined adjacency (EbscoHost platform); TX = free text; EBM = Evidence Based Medicine; EMBASE = Excerpta Medica database; DE = subject heading; DSR = Database of Systematic Reviews; ACP = American College of Physicians; DARE = Database of Abstracts of Reviews of Effects; CCTR = Cochrane Controlled Trials Register; CMR = Cochrane Methodology Register; HTA = Health Technology Assessment; NHSEED = National Health Service Economic Evaluation Database. alimits applied to all searches: human and abstracts. b duplicate references not removed. c search strategy for Ovid platform. d updated search strategy for EbscoHost platform. e includes Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED.

APPENDICES 248

Appendix H – Non-English Articles

Language Yield

Bulgarian 1 ref

Chinese 1 ref

Croatian 1 ref

Czechoslovakian 1 ref

French 3 ref

German 9 ref

Hebrew 1 ref

Japanese 4 ref

Korean 1 ref

Russian 1 ref

Spanish 4 ref

Turkish 2 ref

Ukrainian 1 ref

Note. Ref = references

APPENDICES 249

Appendix I - Handsearched Journals and Reference Yield

Journal Yield

Acta Anaesthesia 3 ref America Journal of Respiratory and Critical Care 1 ref American Journal of Roentgeneology 6 ref Anaesthesia 0 ref Anaesthesia and Analgesia 3 ref Annals of Thoracic Surgery 5 ref Archives of Surgery 1 ref Canadian Journal of Surgery 1 ref Chest 6 ref Circulation 0 ref Critical Care Medicine 0 ref Dysphagia 9 ref Heart and Lung Journal of Acute and Critical Care 4 ref Intensive Care Medicine 0 ref Journal of Anesthesia 0 ref Journal of Trauma 7 ref Radiographics 0 ref Radiology 1 ref The American Journal of Cardiology 1 ref The Journal of Thoracic and Cardiovascular Surgery 0 ref

Note. Search strategy included the following terms: deglutition, deglutition disorder*, dysphagia, intubat*, swallow*; * denotes truncated term ; ref = references

APPENDICES 250

Appendix J – Dysphagia Licenses

APPENDICES 251

APPENDICES 252

APPENDICES 253

APPENDICES 254

Appendix K – Data Abstraction Manual

RA’s Guide to Review of TWH Medical Records Dysphagia Frequency Following Extubation

Order of Chart Review-Sections Start 1. Confirm patient’s age and date of admission with spreadsheet 2. View Scanned Documents a. ICU Flow Sheet – Cardiac (CV Flow) from date of OR date/time of extubation(s) and tracheostomy found here (if date and time of tracheostomy earlier than in DO (below), change to this time), feeding method post-extubation also captured here b. Doctor’s Orders (DO/MD Scan) Diet and tube feeding orders may be found here (record date of referral/orders, if earlier than in CV Flow above, change to this date) c. Doctor’s Orders  SLP referral or diet orders may be found here (record date of referral/orders) d. Doctor’s Orders  SLP suggestions (if SLP suggestions found to be earlier here change date) e. Doctor’s Orders  Tracheostomy order found here (record date/time if available) f. Clinical Notes (CN) SLP suggestions if not recorded in the DO 3. Chart Review a. Nutrition Record diet order and date/time for 96 hours following each extubation

Finish

1. Airway Data

1A. When was the patient extubated? - This info will be found in the ICU Flow Sheet – Cardiac. You must find the note that corresponds with the OR date listed on the database sheet.

a. Find the first CVICU flow sheet following OR date. The ventilation data is captured on the third sheet for that date. It contains the vent settings as well as extubation time at the top. If the extubation time is not captured, the patient was either: 1) not extubated on that day or 2) extubation time is captured on the grid below. The second row of the flow grid contains the mode of ventilation. Mechanical ventilation modes include: AC, PS, PV, PC, CPAP. The patient will be extubated if modes include: FM, NP, SP. When modes change as previously listed, patient will have been extubated and time will be recorded along the top of the grid. Review 96 hours following each extubation.

b. If the patient was intubated/extubated multiple times, record the date and time of each using the methods listed above.

APPENDICES 255

1B. When did the patient receive a tracheostomy? - This info will be found in the ICU Flow Sheet – Cardiac and in the Doctor’s Orders.

a. During the review of extubation(s), if the patient received a trach, it will be documented at the top of the flow sheet, rather than ETT circled, trach will be circled. Vent modes will also be adjusted and may be listed at TP, TM. Also, find the first order for trach in the scanned Doctor’s Orders. Record the earliest date/time listed in either the ICU Flow notes or DOs.

2. Dysphagia Data - This info will be primarily found in the “View Scanned Documents” - Doctor’s Orders, ICU Flow Sheet – Cardiac, or Clinical Notes. Be sure to review orders 96 hours following each extubation.

2A. Was there a new or continuing order for alternative to oral feeding following extubation?

Doctor’s notes could be documented in: i. Doctor’s Orders ii. Clinical Notes iii. Consultation Form iv. Chart Review – Radiology a. Doctor ordered a feeding tube:

First, look in the doctor’s orders. This type of intervention should be in the orders and may have been initially ordered previous to the extubation. The patient has tube feeding as some orders throughout admission may be written as “hold feeds prior to extubation”. Restart/resume feeds will then be written following extubation.

Second, look in the ICU Flow – Cardiac nursing notes. On the first page of that particular day of hospitalization, there is a section entitled “gastrointestinal”. The nurse will document in that section the feeding method or the diet that was administered to the patient if any.

If it is not in the orders or CV Flow, look in the patient’s electronic record (chart review section) under radiology (#7), to find surgical reports (PEG or PEG-J) or chest x- rays (used to confirm placement of NG or OG tube) shortly after extubation.

Feeding Tube Terms: i. orogastric feeding tube, orogastric tube, OG tube, OGT, or OG ii. nasogastric feeding tube, nasogastric tube, NG Tube, NGT, or NG iii. percutaneous endoscopic gastrostomy, or PEG tube or PEG iv. jejunostomy tube or JG tube or J tube or PEG-J or J-PEG

APPENDICES 256 b. Feeding tube was inserted:

NGT or OGT: Look for nursing notes (in Clinical Notes) to find a report that a tube was inserted. If you do not find a nursing note, then look in the electronic record under radiology (#7) if not done in step a. Find a chest x-ray that confirms tube placement.

PEG or PEG-J: Look first in the electronic record under radiology (#7) if not done in step a. Find a surgical report that describes tube placement. This will tell you for sure if a PEG or PEG-J was inserted. The word ‘jejunostomy’ or ‘jejunum’ will mean it is a PEG-J.

It is possible that a nurse may have not entered the information that an NG or OG tube was inserted. Also, chest x-rays don’t always happen or they are not clear.

Last Check: You can also look in the Nutrition section to confirm alternative to oral feeding, because the dietician orders the feeds and the formula. Formulae could be listed as Isosource, Resource, Novasource.

2B. Was there an NPO and swallowing assessment/SLP to see/special swallow study order? AND 2C. Was there an order for SLP to see/speech to see/special swallow study? - This info will be primarily found in the “View Scanned Documents” - Doctor’s Orders. Be sure to review orders 96 hours following each extubation.

a. This will likely be found in the doctor’s orders or a doctor’s note in the Clinical Notes (interdisciplinary section) of scanned documents. Doctor’s orders may say “SLP to see”, “SLP to assess”, “swallowing assessment”, “swallow study/SS”, “speech to see/assess”, “Cookie Swallow”, “VFSS”, “MBS”, “VFS” – any one of these would indicate that a referral to Speech Language Pathology has been made. b. When recording SLP suggest orders, only document the diet or tube feeding order. c. If an “SLP to see” order was written, however, no further orders were written by the SLP, confirm lack of SLP involvement by scanning Clinical Notes for SLP/Swallowing entry.

2D. Did SLP or medical staff recommend modified textures? -This info will be primarily found in the “View Scanned Documents” - Doctor’s Orders. Be sure to review orders 96 hours following each extubation.

a. This will likely be found in the doctor’s orders or a doctor’s note in the Clinical Notes (interdisciplinary section) of scanned documents. Modified textures may be listed as: i. dysphagia diet ii. honey thick liquid iii. nectar thick liquid iv. pudding thick liquid v. pureed diet vi. thickened liquid

APPENDICES 257

vii. minced solids or minced texture viii. dental soft solids or soft solids ix. no mixed textures x. no particulate matter

AND/OR SLP may also recommend or order: i. Nil per os (NPO) ii. Nothing by mouth iii. No food or liquid by mouth iv. Clear Fluids v. Full Fluids

2E. Was the first diet order following extubation for an oral diet?

a. This info will be primarily found in the “View Scanned Documents” - Doctor’s Orders. Be sure to review orders 96 hours following each extubation. The diet orders may also only be captured in the nutrition section below. If this is the case, draw an arrow from this section to the nutrition section on the data abstraction form.

Nutrition Notes Confirmation

List diet orders, date and time (brk, lun, sup) during the first 96 hours following each extubation. Itemize the corresponding diet orders with extubation number (i.e, for the first extubation list diet orders under #1). Diets listed may be recorded with the following abbreviation on the data abstraction form if applicable: Clear Fluids: CF Full Fluids: FF Therapeutic no added sugar 1800Kcal, Heart Healthy etc.: DAT

Chart Location Shorthand Notation If the note was found in: Scanned Doctor’s Orders then write MD Scan ICU Flow Sheet – Cardiac then write CV Flow

APPENDICES 258 Appendix L – Medical Record Review Form

Date of Chart Review:______Name of Reviewer: ______

PATIENT CODE: ______Admission Date: ______1. Airway data 1a. When was the patient extubated? 1 2 Date and time of reintubation: 3 Date and time of reintubation: ______s n r d d Give date and time of FIRST (dd/mm/yy;hr:min) t (dd/mm/yy;hr:min) order: nd Date and time of 2 extubation: rd ______Date and time of 3 extubation: ______(dd/mm/yy;hr:min) (dd/mm/yy;hr:min) (dd/mm/yy;hr:min)  give chart location of first note  give chart location of note ______ give chart location of note ______

1b. Was there a physician order for tracheotomy? Yes No  if ‘no’ skip to 2a  if ‘yes’ give date and time of FIRST order: ______(dd/mm/yy;hr:min)  if ‘yes’, give chart location of first note ______2. Dysphagia data – within first 96 hours post-extubation 2a. Was there a new or continuing order for alternative to oral feeding (i.e. tube feeding [NG, NJ, PEG], TPN, PPN) following extubation? 1 Yes 2 Yes 3 Yes s No  if ‘no’ skip to 2c n No r No  if ‘yes’ give date and time of d  if ‘yes’ give date and time of first d  if ‘yes’ give date and time of t first note ______note______first note ______(dd/mm/yy;hr:min) (dd/mm/yy;hr:min) (dd/mm/yy;hr:min)  if ‘yes’, give chart location of first   if ‘yes’, give chart location of if ‘yes’, give chart location of note first note first note ______

2b. Was there was an NPO and swallowing assessment/SLP to see/special swallow study order? 1 Yes 2 Yes 3 Yes n r s No  if ‘no’ skip to 2c No No d d  if ‘yes’ give date and time of t first note  if ‘yes’ give date and time of  if ‘yes’ give date and time of first note ______first note______(dd/mm/yy;hr:min) (dd/mm/yy;hr:min) (dd/mm/yy;hr:min)  if ‘yes’, give chart location of  if ‘yes’, give chart location of  if ‘yes’, give chart location of first note first note first note ______

APPENDICES 259

2c. Was there an order for SLP to see/speech to see/special swallow study? 1 Yes 2 Yes 3 Yes s No  if ‘no’ skip to 2c n No r No d d  if ‘yes’ give date and time of t first note  if ‘yes’ give date and time of  if ‘yes’ give date and time of first note ______first note______(dd/mm/yy;hr:min) (dd/mm/yy;hr:min) (dd/mm/yy;hr:min)   if ‘yes’, give chart location of  if ‘yes’, give chart location of if ‘yes’, give chart location of first note first note first note ______ if ‘yes’, what did SLP suggest  if ‘yes’, what did SLP suggest  if ‘yes’, what did SLP suggest ______

2d. Did SLP or medical staff recommended modified texture(s)? 1 Yes 2 Yes 3 Yes s No  if ‘no’ skip to 2c n No r No  if ‘yes’ give date and time of d  if ‘yes’ give date and time of d  if ‘yes’ give date and time of t first note ______first note______first note ______(dd/mm/yy;hr:min) (dd/mm/yy;hr:min) (dd/mm/yy;hr:min)  if ‘yes’, give chart location of  if ‘yes’, give chart location of  if ‘yes’, give chart location of

first note first note first note ______2e. Was the first diet order following extubation for an oral diet? 1 Yes 2 Yes 3 Yes s No  if ‘no’ skip to 2c n No r No  if ‘yes’ give date and time of d  if ‘yes’ give date and time of d  if ‘yes’ give date and time of t first note ______first note______first note ______

(dd/mm/yy;hr:min) (dd/mm/yy;hr:min) (dd/mm/yy;hr:min)

 if ‘yes’, give chart location of  if ‘yes’, give chart location of  if ‘yes’, give chart location of

first note first note first note ______

NUTRITION NOTES (list diet orders, date and time during first 96 hours following corresponding extubation): #1 #2 #3

APPENDICES 260

Appendix M – Retrospective Study Sample Size Estimation

In order to determine the sample size required to capture sufficient event rates in the intubation groups, our sample size estimation for our retrospective study was conducted using information from the study conducted by Barker and colleagues (2009). This study was conducted at the same institution using similar inclusion and exclusion criteria. They reported that 2033 cardiovascular surgeries were completed per annum and of those, 85 patients annually required intubation for longer than 48 hours. Of those, 51% had dysphagia. Of the 85 patients,

61 met our study’s inclusion criterion, which thereby comprises 3% of the total population. Base on this estimate of dysphagia and using the formula below (Aday & Cornelius, 2006; Lemeshow, et al., 1990), we calculated a minimum sample size of 26 patients for the >48h stratum which would require a total sample population of 900 patients (α = .05, β = .20).

n = z2 1-α/2 P(1-P) ______

APPENDICES 261

Appendix N – Characteristics of Intubation Stratum I

A. Pre-operative demographics and presenting clinical characteristics for patients intubated <12h

With All patients Without Dysphagia Dysphagia Variable (n = 699) (n = 692) (n = 7)

Age [mean (SD)] (yrs) 64.89 (12.08) 64.79 (12.08) 75.14 (7.18)

[median (IQR)] (yrs) 66.0 (17.0) 65.5 (17) 76.0 (15)

Male, [n (%)] 509 (72.8) 503 (72.7) 6 (58.7)

Family history of heart 373 (53.4) 369 (53.3) 4 (57.1) diseasea, [n (%)]

Diabetes Risksb

Insulin-controlled diabetes 47 (6.7) 45 (6.5) 2 (28.6) mellitus, [n (%)]

Oral hypoglycemics, 156 (22.3) 154 (22.2) 2 (28.6) [n (%)]

Cardiovascular Surgical Risks

Circulatory shock, 5 (0.7) 5 (0.7) 0 (0.0) [n (%)]

Non-Q-wave infarction, 93 (13.3) 92 (13.3) 1 (14.3) [n (%)]

Q-wave infarction, [n (%)] 9 (1.3) 9 (1.3) 0 (0.0)

LV gradec 1, [n (%)] 476 (68.1) 474 (68.5) 2 (28.6) 2, [n (%)] 144 (20.6) 140 (20.2) 4 (57.1) 3, [n (%)] 73 (10.4) 73 (10.5) 0 (0.0) 4, [n (%)] 3 (0.4) 2 (0.3) 1 (14.3)

NYHA classificationd I, [n (%)] 117 (16.7) 116 (16.8) 1 (14.3) II, [n (%)] 156 (22.3) 156 (22.5) 0 (0.0) III, [n (%)] 226 (32.3) 223 (32.2) 3 (42.9) IV, [n (%)] 194 (27.8) 191 (27.6) 3 (42.9)

Congestive heart failure, 106 (15.2) 104 (15.0) 2 (28.6) [n (%)]

Hypertensive, [n (%)] 493 (70.5) 487 (70.4) 6 (85.7)

APPENDICES 262

With All patients Without Dysphagia Dysphagia Variable (n = 699) (n = 692) (n = 7)

Diet or medically-treated 502 (71.8) 495 (71.5) 7 (100.0) hyperlipidemiae, [n (%)]

Previous stroke or TIA, 58 (8.3) 56 (8.1) 2 (28.6) [n (%)]

Normal sinus rhythm, 651 (93.1) 644 (93.1) 7 (100.0) [n (%)]

Heart block / pacemaker, 9 (1.3) 9 (1.3) 0 (0.0) [n (%)]

Atrial fibrillation or flutter, 39 (5.6) 39 (5.6) 0 (0.0) [n (%)]

Left main artery stenosis, 152 (21.7) 151 (21.8) 1 (14.3) [n (%)]

Respiratory Risksf

Smoker, [n (%)] 83 (11.9) 83 (12.0) 0 (0.0)

Ex-Smoker, [n (%)] 318 (45.5) 313 (45.2) 5 (71.4)

Severe COPD, 21 (3.0) 21 (3.0) 0 (0.0) [n (%)]

Renal Risks

Serum creatinine [mean (SD)] (µmol/L) 87.71 (56.94) 87.71 (57.18) 88.29 (26.27) [median (IQR)](µmol/L) 78.0 (24.0) 78.0 (24.0) 95.0 (38.0)

Estimated creatinine clearance 88.78 (32.63) 88.88 (32.58) 78.73 (38.37) [mean (SD)] [median (IQR)] 86.80 (43.64) 86.82 (43.49) 62.56 (77.54)

Note. SD = standard deviation; yrs = years; IQR = interquartile range; LV = left ventricular; NYHA = New York Heart Association; TIA = transient ischemic attack; COPD = chronic obstructive pulmonary disease; µmol/L = micromol per liter. a missing data: 7 patients without dysphagia, 1 patient with dysphagia. b missing data: 1 patient without dysphagia. c missing data: 3 patients without dysphagia. d missing data: 6 patients without dysphagia. e missing data: 1 patient without dysphagia f missing smoking history data: 1 patient with dysphagia.

APPENDICES 263

B. Peri-operative characteristics for patients intubated <12h

Without All patients With Dysphagia Dysphagia Variable (n=699) (n=7) (n=692)

Procedure CABG, [n (%)] 444 (63.5) 438 (63.3) 6 (85.7) Valve, [n (%)] 255 (36.5) 254 (36.7) 1 (14.3)

Urgency Elective, [n (%)] 457 (65.4) 453 (65.5) 4 (57.1) Inpatient, [n (%)] 197 (28.2) 194 (28.0) 3 (42.9) Urgent, [n (%)] 37 (5.3) 37 (5.3) 0 (0.0) Emergent, [n (%)] 8 (1.1) 8 (1.2) 0 (0.0)

CPB 635(90.8) 629 (90.9) 6 (85.7)

CPB duration [mean (SD)] (min) 80.55(38.15) 80.64 (38.18) 71.57 (35.95) [median (IQR)] (min) 82.0 (41.0) 82.0 (41.0) 77.0 (33.0)

TEE, [n (%)] 304 (44.9) 303 (43.7) 1 (64.7)

Perioperative Complications

Stroke, [n (%)] 3 (0.4) 3 (0.4) 0 (0.0)

Sepsis, [n (%)] 5 (0.7) 4 (0.6) 1 (14.3)

Use of dopamine in ICU, 233 (33.3) 232(33.5) 1 (14.3) [n (%)]

MI, [n (%)] 7 (1.0) 7 (1.0) 0 (0.0)

Low-output syndrome, 2 (0.3) 2 (0.3) 0 (0.0) [n (%)]

IABP usage

Pre-operative, [n (%)] 6 (0.9) 6 (0.9) 0 (0.0) Peri-operative, [n (%)] 1 (0.1) 1 (0.1) 0 (0.0) Post-operative, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0)

Note. CABG = coronary artery bypass graft; CPB = cardiopulmonary bypass; SD = standard deviation; IQR = interquartile range; min = minutes; TEE = transeophageal echocardiogram; ICU = intensive care unit; MI = myocardial infarction; IABP = intraaortic balloon pump.

APPENDICES 264

C. Post-operative patient outcomes for patients intubated <12h

Without With All patients Dysphagia Dysphagia Variable (n=699) (n=692) (n=7)

Post-operative atrial 238 (34.0) 233 (33.7) 5 (71.4) fibrillation

Intubation duration [mean (SD)] (h) 6.37 (2.17) 6.38 (2.18) 6.31 (1.46)

[median (IQR)] (h) 6.08 (3.0) 6.04 (3.04) 6.42 (1.92)

Reintubation, [n (%)] 5 (0.7) 4 (0.6) 1 (14.3)

Number of intubations 1, [n (%)] 694 (99.3) 688 (99.4) 6 (85.7) 2, [n (%)] 5 (0.7) 4 (0.6) 1 (14.3) 3, [n (%)] 0 (0.1) 0 (0.0) 0 (0.0) 4, [n (%)] 0 (0.1) 0 (0.0) 0 (0.0)

Re-operation, [n (%)] 7 (1.0) 7 (1.0) 0 (0.0)

Post-extubation repeat ICU 8 (1.1) 8 (1.2) 0 (0.0)

Admission, [n (%)]

ICU stay

[mean (SD)] (h) 44.40 (38.06) 44.27 (37.78) 57.22 (62.63)

[median (IQR)](h) 25.50 (29.08) 25.5 (28.8) 25.33 (56.72)

Preoperative hospital stay [mean (SD)] (d) 1.26 (3.22) 1.25 (3.22) 2.14 (3.02)

[median (IQR)] (d) 1.0 (1.0) 1.0 (1.0) 1.0 (6.0)

Postoperative hospital stay [mean (SD)] (d) 7.33 (3.44) 7.27(3.35) 13.43 (6.35)

[median (IQR)] (d) 6.0 (3.0) 6.0 (3.0) 11.0 (13.0)

Total inpatient stay [mean (SD)] (d) 8.92(5.70) 8.87 (5.7) 14.0 (4.24) [median (IQR)] (d) 7.0 (4.0) 7.0 (4.0) 14.0 (7.0)

Note. SD = standard deviation; h = hours; IQR = interquartile range; ICU = intensive care unit; d = days.

APPENDICES 265

Appendix O – Characteristics of Intubation Stratum II

A. Pre-operative demographics and presenting clinical characteristics for patients intubated >12h and ≤ 24h

Without With All patients Dysphagia Dysphagia (n = 134) Variable (n = 123) (n = 11)

Age [mean (SD)] (yrs) 68.22 (11.84) 67.22 (11.67) 79.36 (7.47)

[median (IQR)] (yrs) 68.5 (15.25) 68.00 (16.0) 81.0 (12.0)

Male, [n (%)] 92 (68.6) 84 (68.3) 8 (72.7)

Family history of heart diseasea, [n 63 (47.0) 59 (48.0) 4 (36.4) (%)]

Diabetes Risks

Insulin-controlled diabetes 13 (9.7) 10 (8.1) 3 (27.3) mellitus, [n (%)]

Oral hypoglycemics, 35 (26.1) 33 (26.8) 2 (18.2) [n (%)]

Cardiovascular Surgical Risks

Circulatory shock, 2 (1.5) 1 (0.8) 1 (9.1) [n (%)]

Non-Q-wave infarction, 22 (16.4) 21 (17.1) 1 (9.1) [n (%)]

Q-wave infarction, 4 (3.0) 3 (2.4) 1 (9.1) [n (%)]

LV gradeb 1, [n (%)] 70 (52.2) 63 (51.2) 7 (63.6) 2, [n (%)] 37 (27.6) 36 (29.3) 1 (9.1) 3, [n (%)] 22 (16.4) 19 (15.4) 3 (27.3) 4, [n (%)] 4 (3.0) 4 (3.3) 0 (0.0)

NYHA classificationc I, [n (%)] 12 (9.0) 12 (9.8) 0 (0.0) II, [n (%)] 21 (15.7) 20 (16.3) 1 (9.1) III, [n (%)] 45 (33.6) 42 (34.1) 3 (27.3) IV, [n (%)] 52 (38.8) 45 (36.6) 7 (63.6)

Congestive heart failure, 31 (23.1) 28 (22.8) 3 (27.3) [n (%)]

Hypertensive, [n (%)] 105 (78.4) 95 (77.2) 10 (90.9)

APPENDICES 266

Without With All patients Dysphagia Dysphagia (n = 134) Variable (n = 123) (n = 11)

Diet or medically-treated 97 (72.4) 90 (73.2) 7 (63.6) hyperlipidemiad, [n (%)]

Previous stroke or TIA, 18 (13.4) 15 (12.2) 3 (27.3) [n (%)]

Normal sinus rhythm, [n (%)] 123 (91.8) 114 (92.7) 9 (81.8)

Heart block / pacemaker, 2 (1.5) 2 (1.6) 0 (0.0) [n (%)]

Atrial fibrillation or flutter, [n (%)] 9 (6.7) 7 (5.7) 2 (18.2)

Left main artery stenosis, [n (%)] 37 (27.6) 32 (26.0) 5 (45.5)

Respiratory Risks

Smoker, [n (%)] 23 (17.2) 23 (18.7) 0 (0.0)

Ex-Smoker, [n (%)] 58 (43.3) 54 (43.9) 4 (36.4)

Severe COPD, [n (%)] 13 (9.7) 13 (10.6) 0 (0.0)

Renal Risks

Serum creatinine [mean (SD)] (µmol/L) 92.79 (41.23) 91.25 (40.35) 110.0 (48.9) [median (IQR) (µmol/L) 83.0 (27.0) 83.0 (26.0) 87.0 (55.0)

Estimated creatinine clearance [mean (SD)] 79.11 (33.54) 81.24 (33.46) 55.22 (24.88) [median (IQR)] 71.89 (39.6) 74.36 (40.02) 48.98 (48.19)

Note. SD = standard deviation; yrs = years; IQR = interquartile range; LV = left ventricular; NYHA = New York Heart Association; TIA = transient ischemic attack; COPD = chronic obstructive pulmonary disease; µmol/L = micromol per liter. a missing data: 1 patient without dysphagia. b missing data: 1 patients without dysphagia. c missing data: 4 patients without dysphagia. d missing data: 1 patient without dysphagia.

APPENDICES 267

B. Peri-operative characteristics for patients intubated >12h and ≤ 24h

Without All patients With Dysphagia Dysphagia (n = 134) (n = 11) Variable (n = 123)

Procedure CABG, [n (%)] 88 (65.7) 83 (67.5) 5 (45.5) Valve, [n (%)] 46 (34.3) 40 (32.5) 6 (54.5)

Urgency Elective, [n (%)] 74 (55.2) 68 (55.3) 6 (54.5) Inpatient, [n (%)] 42 (31.3) 38 (30.9) 4 (36.4) Urgent, [n (%)] 15 (11.2) 14 (11.4) 1 (9.1) Emergent, [n (%)] 3 (2.2) 3 (2.4) 0 (0.0)

CPB 118 (88.1) 112 (91.1) 6 (54.5)

CPB duration [mean (SD)] (min) 88.94 (48.51) 90.75 (45.67) 68.73 (73.28) [median (IQR)] (min) 92.0 (51.25) 92.0 (47.0) 69.0 (123.0)

TEE, [n (%)] 59 (44.0) 51 (41.5) 8 (72.7)

Perioperative Complications

Stroke, [n (%)] 1 (0.7) 0 (0.0) 1 (9.1)

Sepsis, [n (%)] 1 (0.7) 1 (0.8) 2 (18.2)

Use of dopamine in ICU, 78 (58.2) 73 (59.3) 5 (45.5) [n (%)]

MI, [n (%)] 1 (0.7) 1 (0.8) 0 (0.0)

Low-output syndrome, [n (%)] 2 (1.5) 2 (1.6) 0 (0.0)

IABP usage

Pre-operative, [n (%)] 4 (3.0) 3 (2.4) 1 (9.1) Peri-operative, [n (%)] 1 (.07) 1 (0.8) 0 (0.0) Post-operative, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0)

APPENDICES 268

C. Post-operative patient outcomes for patients intubated >12h and ≤ 24h

Without All patients With Dysphagia Dysphagia (n = 134) (n = 11) Variable (n = 123)

Post-operative atrial 58 (47.2) 52 (42.3) 6 (54.5) fibrillation

Intubation duration [mean (SD)] (h) 16.86 (3.13) 16.80 (3.07) 17.66 (3.81)

[median (IQR)] (h) 16.5 (4.7) 16.50 (4.6) 17.83 (6.82)

Reintubation, [n (%)] 4 (3.0) 4 (3.3) 0 (0.0)

Number of intubations 1, [n (%)] 130 (97.0) 119 (96.7) 11 (100.0) 2, [n (%)] 4 (3.0) 4 (3.3) 0 (0.0) 3, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0) 4, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0)

Re-operation, [n (%)] 14 (10.4) 14 (11.4) 0 (0.0)

Post-extubation repeat ICU 10 (7.5) 8 (6.5) 2 (18.2) admission, [n (%)]

ICU stay [mean (SD)] (h) 81.52 (70.49) 77.60 (66.14) 125.34 (102.02)

[median (IQR)] (h) 67.49(54.0) 66.17 (52.42) 116.50 (93.25)

Preoperative hospital stay [mean (SD)] (d) 1.13 (1.85) 1.04 (1.69) 2.18 (3.06)

[median (IQR)] (d) 1.0 (1.0) 1.0 (1.0) 1.0 (3.0)

Postoperative hospital stay [mean (SD)] (d) 10.74 (7.60) 9.61(5.10) 23.36 (16.10)

[median (IQR)] (d) 8.0 (5.0) 8.0 (4.0) 17.0 (19.0)

Total inpatient stay [mean (SD)] (d) 11.43 (7.49) 10.8 (7.09) 18.36 (8.58) [median (IQR)] (d) 9.0 (6.0) 9.0 (5.0) 15.0 (9.0)

Note. SD = standard deviation; h = hours; IQR = interquartile range; ICU = intensive care unit; d = days.

APPENDICES 269

Appendix P – Characteristics of Intubation Stratum III

A. Pre-operative demographics and presenting clinical characteristics for patients intubated >24h and ≤48h

Without With All patients Dysphagia Dysphagia Variable (n = 36) (n = 30) (n = 6)

Age [mean (SD)] (yrs) 70.81 (11.72) 70.53 (11.81) 72.17 (12.22)

[median (IQR)] (yrs) 75.0 (16.25) 74.5 (15.0) 76.5 (22.0)

Male, [n (%)] 23 (63.9) 17 (56.7) 6 (100.0)

Family history of heart 19 (52.8) 14 (46.7) 5 (83.3) disease, [n (%)]

Diabetes Risks

Insulin-controlled 5 (13.9) 5 (16.7) 0 (0.0) diabetes mellitus, [n (%)]

Oral hypoglycemics, 10 (27.8) 9 (30.0) 1 (16.7) [n (%)]

Cardiovascular Surgical Risks

Circulatory shock, [n (%)] 2 (5.6) 2 (6.7) 0 (0.0)

Non-Q-wave infarction, 7 (19.4) 6 (20.0) 1 (16.7) [n (%)]

Q-wave infarction, 1 (2.8) 1 (3.3) 0 (0.0) [n (%)]

LV grade 1, [n (%)] 14 (38.9) 12 (40.0) 2 (33.3) 2, [n (%)] 16 (44.4) 13 (43.3) 3 (50.0) 3, [n (%)] 5 (13.9) 4 (13.3) 1 (16.7) 4, [n (%)] 1 (2.8) 1 (3.3) 0 (0.0)

NYHA classification I, [n (%)] 1 (2.8) 1 (3.3) 0 (0.0) II, [n (%)] 6 (16.7) 6 (20.0) 0 (0.0) III, [n (%)] 8 (22.2) 4 (13.3) 4 (66.7) IV, [n (%)] 21 (58.3) 19 (63.3) 2 (33.3)

Congestive heart failure, 12 (33.3) 8 (26.7) 4 (66.7) [n (%)]

Hypertensive, [n (%)] 25 (69.4) 22 (73.3) 3 (50.0)

APPENDICES 270

Without With All patients Dysphagia Dysphagia Variable (n = 36) (n = 30) (n = 6)

Diet or medically-treated 29 (80.6) 26 (86.7) 3 (50.0) hyperlipidemia, [n (%)]

Previous stroke or TIA, 3 (8.3) 3 (10.0) 0 (0.0) [n (%)]

Normal sinus rhythm, 27 (75.0) 22 (73.3) 5 (83.3) [n (%)]

Heart block / pacemaker, 6 (16.7) 6 (20.0) 0 (0.0) [n (%)]

Atrial fibrillation or 3 (8.3) 2 (6.7) 1 (16.7) flutter, [n (%)]

Left main artery stenosis, 11 (30.6) 10 (33.3) 1 (16.7) [n (%)]

Respiratory Risksa

Smoker, [n (%)] 2 (5.6) 0 (0.0) 2 (33.3)

Ex-smoker, [n (%)] 19 (52.8) 17 (56.7) 2 (33.3)

Severe COPD, 1 (2.8) 1 (3.3) 0 (0.0) n (%)

Renal Risks

Serum creatinine [mean (SD)] (µmol/L) 90.06 (23.14) 87.0 (21.94) 105.33 (24.91) [median (IQR)] (µmol/L) 89.5 (28.25) 87.0 (30.0) 115.50 (51.0)

Estimated creatinine clearance [mean (SD)] 74.6 (30.79) 75.14 (29.52) 71.90 (39.65) [median (IQR)] 70.29 (37.47) 72.97 (37.72) 53.52 (60.55)

APPENDICES 271

B. Peri-operative characteristics for patients intubated >24h and ≤48h

Without With All patients Dysphagia Dysphagia Variable (n = 36) (n = 30) (n = 6)

Procedure CABG, [n (%)] 16 (62.4) 15 (63.8) 1 (39.2) Valve, [n (%)] 20 (37.6) 15 (36.2) 5 (60.8)

Urgency Elective, [n (%)] 20 (55.6) 17 (56.7) 3 (50.0) Inpatient, [n (%)] 12 (33.3) 9 (30.0) 3 (50.0) Urgent, [n (%)] 3 (8.3) 3 (10.0) 0 (0.0) Emergent, [n (%)] 1 (2.8) 1 (3.3) 0 (0.0)

CPB 35 (97.2) 29 (96.7) 6 (100.0)

CPB duration [mean (SD)] (min) 111.31 (37.75) 108.47 (39.07) 125.50 (28.82) [median (IQR)] (min) 110.5 (43.75) 101.50 (42.0) 130.0 (49.0)

TEE, [n (%)] 24 (66.7) 18 (60.0) 6 (100.0)

Perioperative Complications

Stroke, [n (%)] 1 (2.8) 0 (0.0) 1 (16.7)

Sepsis, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0)

Use of dopamine in ICU, 367 (40.4) 339 (39.5) 28 (54.9) [n (%)]

MI, [n (%)] 28 (77.8) 23 (76.7) 5 (83.3)

Low-output syndrome, [n (%)] 7 (2.2) 7 (1.5) 0 (13.7)

IABP usage

Pre-operative, [n (%)] 4 (11.1) 4 (13.3) 0 (0.0) Peri-operative, [n (%)] 6 (16.7) 6 (20.0) 0 (0.0) Post-operative, [n (%)] 1 (2.8) 1 (3.3) 0 (0.0)

APPENDICES 272

C. Post-operative patient outcomes for patients intubated >24h and ≤48h

Without With All patients Dysphagia Dysphagia Variable (n = 36) (n = 30) (n = 6)

\ Post-operative atrial 24 (66.7) 21 (70.0) 3 (50.0) fibrillation

Intubation duration [mean (SD)] (h) 33.94 (7.77) 32.32 (7.4) 42.08 (3.17)

[median (IQR)] (h) 33.04 (13.6) 30.25 (13.17) 41.46 (5.89)

Reintubation, [n (%)] 2 (5.6) 2 (6.7) 0 (0.0)

Number of intubations 1, [n (%)] 34 (94.4) 28 (93.3) 6 (100.0) 2, [n (%)] 2 (5.6) 2 (6.7) 0 (0.0) 3, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0) 4, [n (%)] 0 (0.0) 0 (0.0) 0 (0.0)

Re-operation, [n (%)] 4 (11.1) 4 (13.3) 0 (0.0)

Post-Extubation Repeat 2 (5.6) 2 (6.7) 0 (0.0) ICU Admission, [n (%)]

ICU stay [mean (SD)] (h) 93.67 (32.38) 90.60 (30.02) 109.02 (29.98)

[median (IQR)] (h) 93.33 (44.23) 90.96 (43.52) 105.21 (53.31)

Preoperative hospital stay [mean (SD)] (d) 1.53 (2.32) 1.20 (1.8) 3.17 (3.97)

[median (IQR)] (d) 1.0 (1.0) 1.0 (1.0) 1.0 (6.0)

Postoperative hospital stay [mean (SD)] (d) 11.28 (8.68) 11.03 (9.38) 12.50 (3.94)

[median (IQR)] (d) 9.0 (2.75) 9.0 (3.0) 12.50 (8.0)

Total inpatient stay [mean (SD)] (d) 11.78 (7.25) 10.4 (4.2) 18.67 (14.05) [median (IQR)] (d) 9.5 (7.75) 9.0 (7.0) 15.0 (21.0)

Note. SD = standard deviation; h = hours; IQR = interquartile range; ICU = intensive care unit; d = days.

APPENDICES 273

Appendix Q – Characteristics of Intubation Stratum IV A. Pre-operative demographics and presenting clinical characteristics for patients intubated >48h

Without With All patients Dysphagia Dysphagia (n = 40) Variable (n = 13) (n = 27)

Age [mean (SD)] (yrs) 72.2 (7.9) 71.4 (7.4) 72.6 (8.3)

[median (IQR)] (yrs) 73.0 (10.8) 71.0 (13.0) 74.0 (11.0)

Male, [n (%)] 25 (62.5) 8 (61.5) 17 (63.0)

Family history of heart 21 (52.5) 7 (53.8) 14 (51.9) disease, [n (%)]

Diabetes Risks

Insulin-controlled diabetes 3 (7.5) 2 (15.4) 1 (3.7) mellitus, [n (%)]

Oral hypoglycemics, [n (%)] 7 (17.5) 3 (23.1) 4 (14.8)

Cardiovascular Surgical Risks

Circulatory Shock, [n (%)] 1 (2.5) 1 (7.7) 0 (0.0)

Non-Q-wave infarction, [n 5 (12.5) 5 (38.5) 0 (0.0) (%)]

Q-wave infarction, [n (%)] 1 (2.5) 1 (7.7) 0 (0.0)

LV grade 1, [n (%)] 22 (55.0) 7 (53.8) 15 (55.6) 2, [n (%)] 10 (25.0) 4 (30.8) 6 (22.2) 3, [n (%)] 7 (17.5) 2 (15.4) 5 (18.5) 4, [n (%)] 1 (2.5) 0 (0.0) 1 (3.7)

NYHA classificationa I, [n (%)] 1 (2.5) 1 (7.7) 0 (0.0) II, [n (%)] 6 (15.0) 1 (7.7) 5 (18.5) III, [n (%)] 16 (40.0) 4 (30.8) 12 (44.4) IV, [n (%)] 16 (40.0) 7 (53.8) 9 (33.3)

Congestive heart failure [n 17 (42.5) 5 (38.5) 12 (44.4) (%)]

Hypertensive, [n (%)] 32 (80.0) 12 (92.3) 20 (74.1)

Diet or medically-treated 30 (75.0) 9 (69.2) 21 (77.8) hyperlipidemia, [n (%)]

Previous stroke or TIA, 9 (22.5) 1 (7.7) 8 (29.6) [n (%)]

APPENDICES 274

Without With All patients Dysphagia Dysphagia (n = 40) Variable (n = 13) (n = 27)

Normal sinus rhythm, 33 (82.5) 13 (100.0) 20 (74.1) [n (%)]

Heart block / pacemaker, 1 (2.5) 0 (0.0) 1 (3.7) [n (%)]

Atrial fibrillation or flutter, 6 (15.0) 0 (0.0) 6 (22.2) [n (%)]

Left main artery stenosis, 9 (22.5) 4 (30.8) 5 (18.5) [n (%)]

Respiratory Risksb

Smoker, [n (%)] 7 (17.5) 3 (23.1) 4 (14.8)

Ex-smoker, [n (%)] 19 (47.5) 5 (38.5) 14 (51.9)

Severe COPD, [n (%)] 3 (7.5) 2 (15.4) 1 (3.7)

Renal Risks

Serum creatinine [mean (SD)] (µmol/L) 107.63 (40.08) 91.54 (26.13) 115.37 (43.61) [median (IQR)] (µmol/L) 96.0 (49.25) 90.0 (47.0) 107.0 (54.0)

Estimated creatinine clearance 61.56(21.79) 75.23 (24.76) 54.98 (17.06) [mean (SD)] [median (IQR)] 56.58 (25.31) 71.21 (38.3) 51.72 (26.98)

APPENDICES 275

B. Peri-operative characteristics for patients intubated >48h

Without With All patients Dysphagia Dysphagia Variable (n = 40) (n = 13) (n = 27)

Procedure CABG, [n (%)] 19 (62.4) 11 (63.8) 8 (39.2) Valve, [n (%)] 21 (37.6) 2 (36.2) 19 (60.8)

Urgency Elective, [n (%)] 23 (57.5) 5 (38.5) 18 (66.7) Inpatient, [n (%)] 12 (30.0) 4 (30.8) 8 (32.1) Urgent, [n (%)] 4 (10.0) 3 (23.1) 1 (3.7) Emergent, [n (%)] 1 (2.5) 1 (7.7) 0 (0.0)

CPB 38 (95.0) 13 (100.0) 25 (92.6)

CPB duration [mean (SD)] (min) 109.03 (53.21) 93.85 (22.51) 116.33 (61.98) [median (IQR)] (min) 94.0 (60.25) 92.0 (22.0) 94.0 (76.0)

TEE, [n (%)] 31 (44.9) 8 (43.7) 23 (64.7)

Perioperative Complications

Stroke, [n (%)] 5 (12.5) 1 (7.7) 4 (14.8)

Sepsis, [n (%)] 1 (0.9) 0 (0.6) 1 (5.9)

Use of dopamine in ICU, [n 28 (70.0) 11 (84.6) 17 (63.0) (%)]

MI, [n (%)] 4 (10.0) 1 (7.7) 3 (11.1)

Low-output syndrome, [n (%)] 9 (22.5) 2 (15.4) 7 (25.9)

IABP usage

Pre-operative, [n (%)] 3 (7.5) 2 (15.4) 1 (3.7) Peri-operative, [n (%)] 5 (12.5) 1 (7.7) 4 (14.8) Post-operative, [n (%)] 2 (5.0) 0 (0.0) 2 (7.4)

REFERENCES 276

C. Post-operative patient outcomes for patients intubated >48h

Without With All patients Dysphagia Dysphagia (n = 40) Variable (n = 13) (n = 27)

Post-operative atrial 22 ( 55.0) 6 (46.2) 16 (59.3) fibrillation

Intubation duration [mean (SD)] (h) 104.1 (43.05) 83.13 (36.34) 114.20 (42.95)

[median (IQR] (h) 89.33 (46.89) 70.5 (34.25) 103.50 (58.25)

Reintubation, [n (%)] 14 (35.0) 3 (23.1) 11 (40.7)

Number of intubations 1, [n (%)] 26 (65.0) 10 (76.9) 16 (59.3) 2, [n (%)] 12 (30.0) 3(23.1) 9 (33.3) 3, [n (%)] 1 (2.5) 0 (0.0) 1 (3.7) 4, [n (%)] 1 (2.5) 0 (0.0) 1 (3.7)

Re-operation, [n (%)] 10 (25.0) 2 (15.4) 8 (29.6)

Post-Extubation Repeat 1 (2.5) 0 (0.0) 1 (3.7) ICU Admission, [n (%)]

ICU stay [mean (SD)] (h) 201.57 (129.36) 142.99 (45.10) 229.77 (147.04)

[median (IQR)] (h) 166.0 (82.66) 119.75 (57.67) 170.67 (133.50)

Preoperative hospital stay [mean (SD)] (d) 1.65 (2.76) 0.54 (0.66) 2.19 (3.21)

[median (IQR)] (d) 1.0 (1.0) 0.0 (1.0) 1.0 (0.0)

Postoperative hospital stay [mean (SD)] (d) 18.7 (11.75) 13.69 (6.20) 21.11 (13.08)

[median (IQR)] (d) 15.0 (9.5) 12.0 (5.0) 15.0 (2.12)

Total inpatient stay [mean (SD)] (d) 17.08 (12.15) 13.31 (13.83) 18.90 (11.07) [median (IQR)] (d) 12.0 (11.25) 10.0 (4.0) 16.0 (11.0)

Note. SD = standard deviation; h = hours; IQR = interquartile range; ICU = intensive care unit; d = days.