A New Modified Evans Blue Dye Test as Screening Test for Aspiration in Tracheostomized Patients

Author’s Accepted Manuscript A New Modified Evans Blue Dye Test as Screening Test for Spiration in Tracheostomized Patients Alfonso Fiorelli, Fausto Ferraro, Francesca Nagar, Pierluigi Fusco, Salvatore Mazzone, Giuseppe Costa, Davide Di Natale, Nicola Serra, Mario Santini

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To appear in: Journal of Cardiothoracic and Vascular Anesthesia Received date: 26 March 2016 Cite this article as: Alfonso Fiorelli, Fausto Ferraro, Francesca Nagar, Pierluigi Fusco, Salvatore Mazzone, Giuseppe Costa, Davide Di Natale, Nicola Serra and Mario Santini, A New Modified Evans Blue Dye Test as Screening Test for Spiration in Tracheostomized Patients, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2016.07.031 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

A NEW MODIFIED EVANS BLUE DYE TEST AS SCREENING TEST FOR SPIRATION IN TRACHEOSTOMIZED PATIENTS

Alfonso Fiorelli1, MD, PhD, Fausto Ferraro2, MD, Francesca Nagar2, MD, Pierluigi Fusco2, MD, Salvatore Mazzone3, MD, Giuseppe Costa3, MD, Davide Di Natale1, MD, Nicola Serra4, PhD, and Mario Santini1, MD

1

Thoracic Surgery Unit, Second University of Naples, Naples, Italy; 2 Anaesthesia and Intesive Care

Unit; Second University of Naples, Naples, Italy; 3Otorhinolaringoatric Unit, Second University of Naples, Naples; Italy; 4Department of Radiology, Second University of Naples, Naples, Italy.

Key words: Modified Evans Blue Dye Test, Fiberoptic Endoscopic Exam of the Swallow, tracheostomy

Corresponding Author: Alfonso Fiorelli MD, PhD Thoracic Surgery Unit, Second University of Naples Piazza Miraglia, 2 I-80138 Naples, Italy Phone: +390815665228 Fax: +390815665230 e-mail: [email protected]

OBJECTIVE: We assessed the diagnostic accuracy of a new Modified Evans Blue Dye Test (MEBDT) as screening test for aspiration in tracheostomized patients.

DESIGN: Monocentric retrospective study performed between October 2013-December 2015

SETTING: Anesthesia and Intensive Care Unit- Second University of Naples

PARTECIPANTS: Among 62 eligible patients, 5 were excluded. Our study population included 57 patients.

INTERVENTIONS: Patients underwent both Fiberoptic Endoscopic Exam of the Swallow (FEES) and MEBDT to evaluate swallow. The MEBDT results were compared with those of FEES and the diagnostic accuracy of MEBDT was calculated using the FEES as gold standard.

MEASUREMENTS AND MAIN RESULTS: We found that both FEES and MEBDT were positive for aspiration in 40 patients (true positive MEBDT); FEES and MEBDT were negative in 10 (true negative MEBDT). On the other hand, FEES was positive with a MEBDT negative in 7 patients (false negative MEBDT), and there were no FEES negative and MEBDT positive (false positive MEBDT). MEBDT had a sensitivity, specificity, positive and negative predicted value of 85%; 100%; 100% and 58.82%.

CONCLUSIONS: MEBDT could be a supplementary diagnostic test for aspiration. Patients with positive MEBDT should not undergo oral feeding while patients with negative MEBDT should undergo FEES before starting oral feeding.

INTRODUCTION Tracheostomy is a common procedure in intensive care patient management. Percutaneous dilatational tracheostomy (PDT) is the preferred technique in the majority of units compared to surgical tracheostomy mainly because PDT is a bedside procedure and a minimally invasive technique [1]. The presence of a tracheotomy tube alone, regardless of the basic disease, influences the swallowing function. Silent aspiration is associated with an increased risk of serious complications such as bronchospasm, pneumonia, and acute respiratory distress syndrome (ARDS) [2,3]. Thus, an accurate swallowing evaluation is mandatory before oral feeding start. Evans Blue Dye Test (EBDT), introduced by Cameron et al. in 1973 [4], is the most popular method for swallowing investigation. Usually, it is performed by placing four drops of 1% solution of Evans blue dye on patient’s tongue every 4 hours and then by aspirating through tracheostomy for 48 hours regularly. If blue colouring is observed during suctioning, the test is considered positive for aspiration. The Modified Evans Blue Dye Test (MEBDT) is a variation of the original EBDT, because it is performed using food materials, such as ice, liquid, or pureed, marked with blue dye. However, several authors [5-8] have found that MEBDT has a lower diagnostic value (ranging from 38% to 79%) than invasive procedures such as Video-fluoroscopic Swallow Study (VFSS) and Fiberoptic Endoscopic Exam of the Swallow (FEES). In the present paper, we evaluated the diagnostic accuracy of a new MEBDT test in comparison to standard FEES for assessing the risk of aspiration in tracheostomized patients.

MATERIAL AND METHODS Study Design This is a monocentric retrospective study performed at the Anesthesia and Intensive Care Unit of the Second University of Naples, from October 2013 to December 2015. Inclusion criteria were all consecutive patients (i) weaned from mechanical ventilation; (ii) aged > 18 years old; (iii) with a wide range of diseases (i.e. brain injury, stroke, cardiac injury, respiratory failure), (iv) undergoing the same type of Percutaneous Dilatational Tracheostomy (PDT) as Ciaglia Blue RhinoTM (Cook, 5690 AE Son, The Netherlands), (v) and without cognitive disorders that make difficult to perform FEES and new MEBD tests. Exclusion criteria were. (i) patients having surgical tracheostomy or PDTs different from Ciaglia Blue-Rhino (i.e. Fantoni technique), or (ii) patients who did not undergo FEES. In agreement with the other previous experiences [2,9-11], a multidisciplinary team including physiotherapists and medical staff decided that patients were fit for swallowing tests. In particular, when they were clinically stable, presented adequate cognitive and alertness levels, had possibility of oral feeding, and were ready to handle the food bolus in the oral cavity. Patients underwent both FEES and MEBDT, in order to evaluate swallowing. The MEBDT results, recorded by a nurse blinded to the FEES results, were compared with FEES results and the accuracy of MEBDT was calculated using FEES as the gold standard. The results of MEBDT did not change the standard diagnostic work and the decision to restart or not oral feeding was made according to FEES results. The study design was approved by Ethics Committee of Second University of Naples. All patients signed an informed consent form for the execution of invasive exams and they were aware that data would have been used for scientific purpose only.

Procedures Modified Evans Blue Dye Test (MEBDT). First of all, three teaspoons of water were put into the mouth and the patient was asked to swallow. In patients who were able to swallow, we could perform the MEBDT test. During the examination, we deflated the cuff and removed the nasogastric tube. Tracheostomy was occluded with speaking valve or by finger to facilitate subglottic pressure increase during swallowing. The patient in sitting position was invited to drink 0.2% methylene blue solution diluted in normal saline through a 50 ml syringe with tapered curved tip. Then, the suction catheter was introduced in the tracheostomy tube and the negative pressure was applied. The tracheal suctioning did not exceed 10 seconds and it was immediately stopped in presence of a decline of oxygen saturation to a level lower than 2% of the initial value or with an increase of heart rate or systolic blood pressure beyond 100 bpm and 180 mm Hg respectively. The specimen was examined under full room lighting and the presence of blue discoloration in secretions indicated the positivity of the test. We carried out the test three times with an interval of at least 24 hours in order to verify whether the swallowing dysfunction (if present) was transient or stable. To avoid any interference between MEBDT carried out during different times, at the end of each test the tracheal cuff was reinflated with the same pre-procedural pressure (17±2.7 cm H2O). In all cases, the cuff pressure did not exceed the 20-25 cm H2O since, as reported by Amathieu et al. [11], these levels could the reflex swallows and depressed the efficiency of sub-mental muscles. MEBDT was considered negative if all three tests were negative for aspiration and positive in case of all three positive tests and/or of mixed results (i.e. two negative and one positive, or two positive and one negative tests). Fiberoptic Endoscopic Exam of the Swallow (FEES). The FEES was performed according to the standard protocol reported by Langmore et al. [12]. It was assessed at least 24 hours after the last

MEBDT and was not repeated. All patients were evaluated at bedside with the upper part of the body being elevated. As for MEBDT, the tracheotomy tube cuff was deflated prior to procedure. The fiberoptic endoscope, lubricated with a non-anaesthetic gel, was passed trans-nasally until the larynx and hypopharynx were visualized. Following, the patient received teaspoon-sized portions of 3 different food consistencies dyed with blue food coloring for ease of visualization. The first food consistency introduced was pureed food, followed by liquid and soft solid food. The food was given in bolus of approximately 3 mL. During the swallow, the tip of the endoscope was placed in the posterior nasopharynx. Immediately after the swallow, the endoscope was advanced into the oropharynx and positioned just above the vocal folds. Aspiration was defined as any material entering the airway below the vocal cords.

Statistical Analysis The sample size was calculated using the Bernoulli method. Considering that the sensitivity of MEBDT test ranged from 38%-79% as reported in previous papers [5-8], we hypothesized a prevalence of expected true positive equal to 59%, with an error of 20% and an Z score at 99%. Thus, the sample size estimated was 50 patients. However, our sample was increased to 62 patients to preserve the statistical significance in the case of patients excluded from the analysis (i.e. lack of data etc…) Data were reported as means ± standard deviation (SD). The diagnostic accuracy of MEBDT was calculated using FEES as the objective measure of aspiration, as follows: (i) FEES and MEBDT positive for aspiration (true positive MEBDT); (ii) FEES and MEBDT negative for aspiration (true negative MEBDT); (iii) FEES positive for aspiration and MEBDT negative for aspiration (false negative MEBDT); and (iv) FEES negative for aspiration and MEBDT positive for aspiration (false positive MEBDT). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% Confidence of Interval (95% CI) were calculated in the standard manner.

MedCalc® statistical software was used for analysis.

RESULTS 62 patients were eligible for the present study. Of these, 5 patients were excluded because they were unable to tolerate (n=4) or refused FEES (n=1). The characteristics of our study population (57 patients) are summarized in Table 1. The mean age was 67 ± 5.7 years; 37 patients were males and 20 were females. The Ciaglia Blue-Rhino PDTs were performed under endoscopic guidance by the same physicians (FF and AF). Patients were hospitalized for respiratory failure (n=25), sepsis (n=9); stroke (n=3); and cardiac injury (n=20). Tracheostomy was performed 10 ± 4.5 days after orotracheal intubation; the days of ventilation post tracheostomy were 27 ±

9.8 days; and

swallowing tests were carried out 13±5 days after weaning from mechanical ventilation. Tracheotomy tube size ranged from six to eight. All patients had adequate bilateral vocal fold mobility. Aspiration on FEES was found in 47/57 (82%) patients. FEES and MEBDT were both positive for aspiration in 40 patients (true positive MEBDT); FEES and MEBDT were both negative for aspiration in 10 patients (true negative MEBDT). FEES positive for aspiration and MEBDT negative for aspiration in 7 patients (false negative MEBDT); and (iv) no case of FEES negative for aspiration and MEBDT positive for aspiration (false positive MEBDT) were found. Thus, MEBDT had a sensitivity of 85% (71.69%-93.80%); a specificity of 100% (69.15%-100%); a PPV of 100% (91.19%-100%) and a NPV of 58.82% (32.92%-81.56%).

Figure 1 is a flow chart

of this study.

DISCUSSION Silent aspiration due to swallowing alterations occurs in 30-50% of patients undergoing tracheostomy [2]. Considering the increasing number of PDT performed every year in Intensive

Care Unit (ICU) and the potential severe complications related to aspiration, it is mandatory to exclude it when tracheostomized patients start oral feeding. Since its introduction almost 30 years ago, the diagnostic accuracy of EBDT and MEBDT test in documenting aspiration has been questioned. Thompson-Henry et al [5] found that five tracheostomized patients with negative MEBDT had aspiration on VFSS. Following, Brady et al. [6] reported that 50% of tracheostomized patients with known aspiration on VFSS resulted to be negative on MEBDT. The lower sensitivity rate of MEBDT (ranging from 38% to 79%) for detecting aspiration compared to VFSS and/or FEES was then confirmed by other authors [7,8]. However, FEES and VFSS remain challenging procedures that need particular skills as the use of bronchoscopy and/or of radiology. Thus, new screening tests, easy to administrate and with better accuracy than standard MEBDT, would be extremely valuable. In the present study, we proposed a new MEBDT to detect aspiration in tracheostomized patients and evaluated its diagnostic accuracy considering FEES as gold standard. Because this is a retrospective study, we included only patients undergoing Ciaglia Blue Rhino PDT in order to have an homogeneous sample size and thus to minimize any variables that could affect our results. Patients with surgical tracheostomy were excluded because the surgical trauma of the neck could affect more seriously swallowing function compared to PDT. Similarly, other PDT procedures (Ciaglia Blue-Rhino, PercuTwist , Fantoni) could differently impact swallowing function due to different strategy for

tracheostomy introduction. Thus, in this study we included patients

undergoing Ciaglia Blue Rhino PDT since this procedure resulted to be less traumatic than others in authors' experience, as recently reported [1,13,14]. Our test differs from previous MEBDTs for the materials used (liquid rather than semisolid or solid) and timing (MEBDT in three different times rather than once). In addition, in our protocol, the ability of patients to swallow was tested before MEBDT by the administration of 3 teaspoons of water and MEBDT was not performed in patients completely unable to swallow.

We found that our test had a sensitivity and specificity of 85% and 100%, respectively. That means that in seven patients aspiration was seen on FEES but it was undetected by MEBDT while all 10 patients with positive MEBDT resulted to have aspiration on FEES test. Despite the specificity value is in line with other reports [15-17], the high sensitivity of our test is in contrast with studies of Donzelli et al. [7], of Brady et al. [6], and of Thompson-Herny et al. [5] who reported a sensitivity of 50% compared to FEES and VEFS test. The different substance used, the time of administration, and the homogeneity of sample population could explain the different results, despite any comparisons with previous studies remain challenging due to the different protocol. MEBDT was performed with semisolid pudding or pureed solids by Brady et al. [6] or Thompson-Herny et al. [5] and this strategy would be less accurate than MEBDT assessed with thin liquid as in our protocol. In addition, in our protocol each patient received three separated new MEBDTs at interval of 24 hours. It allowed to verify whether the swallowing dysfunction was transient or stable with consequent reduction of the number of false negative and false positive results. Patients with swallowing disorders often exhibit highly variable swallowing patterns, so it is not unusual that the same patient presents aspiration only once with the same conditions. Similarly, Belfasky et al. [4] performed MEBDT test three times (30 and 60 minutes after the first test) and reported a sensitivity of 82%. The same original technique of Cameron et al. [4] consisted of administering the dye every 4 hours for 48 hours. Thus, performing the test only once as described by Donzelli et al. [5] and Brady et al. [6] could limit its sensitivity. Only one patient in our study population presented neurological disease while the sample size of Donzelli et al. [5] and Brady et al. [6] presented heterogeneous neurological diseases that may in part explain the presence of dysphagia. Winklmaier et al. [17] reported a sensitivity of 95.24% and a specificity of 100% in a sample population of tracheostomized patients after treatment of head and neck squamous carcinoma suggesting that the sensitivity is much better preserved in homogenous cohort of patients than expected.

The airway protection during oral feeding in tracheostomized patient is a current controversial issue. Some physicians start oral feeding without any hesitation and stop it when symptoms appear while others are against oral feeding in almost every patients. However, both strategies are questionable because the first could expose patient to severe complications due to aspiration while the second could limit patient’s return to usual activities. Thus, a shared approach could be used to assess the presence of aspiration before starting oral feeding. In this setting, our MEBDT could be a valid extra test to standard exams in clinical practice as summarized by a simple flow chart reported in Figure 2. The low Negative Predict Value of our MEBDT (ability to correctly predict the absence of aspiration) indicates that all patients with negative MEBDT should always undergo instrumental exams as FEES and/or VFSS before starting oral feeding in order to confirm the absence of aspiration. On the other hand, the 100% value of Predictive Positive Value (ability to correctly predict the presence of aspiration) observed in our study assures that patients with positive MEBDT test have aspiration. In these cases, additional invasive and expensive tests as FEES and /or VEFS are not necessary. From a clinical point of view, in patients with positive MEBDT and in those positive on FEES, Percutaneous Endoscopic Gastrostomy (PEG) could be a valid alternative to nasogastric feedings to reduce the risk of complications related to aspiration. There is evidence in literature that the presence of a nasogastric feeding tube is responsible of aspiration pneumonia due to several mechanisms including (i) loss of anatomical integrity of the upper and lower esophageal sphincters; (ii) increase in the frequency of transient lower esophageal sphincter relaxations, and (III) desensitization of the pharyngo-glottal adduction reflex [11,18]. In a Cochrane review of 2012, Gomes et al. [19] evaluated the results from nine controlled studies comparing a nasogastric tube with PEG in a total of 686 patients. The study showed a higher probability of treatment failure and development of pneumonia with the use of a nasal gastric tube. The number of deaths was no different with the two methods; nor was the overall occurrence of complications. The update of this review, performed by the same authors in 2015 [20],

confirmed that PEG was associated with a lower probability of intervention failure but without any differences on mortality rates and adverse events, including pneumonia related to aspiration. These data are in line with Stroud et al [21] who reported that PEG feeding could reduce but not eliminate the risk of aspiration. Obviously, our data should be considered with caution due to several limitations. Because the MEBDTs were performed in three different occasions, it was not possible to simultaneously administer the MEBDT and the FEES and this time bias could have affected the results. In line with Belafsky et al. [15] and Winklmaier et al. [17] we did not measure the amount of aspiration (i.e. a small amount or a measurable quantity) and it could explain the 40% rate of aspiration seen in our population. Despite aspiration is a well-known risk factor for pneumonia, the present study is unable to define whether the aspiration detected in our patients was associated with the increasing risk of pneumonia or other complications. In conclusion, our MEBDT is easy to use, economic and very well tolerated. It should be considered not as an alternative to standard diagnostic invasive exams but as a screening tool to identify which tracheostomized patients should undergo FEES or VFSS. According our results, patients with positive MEBDT should not undergo oral feeding and could be candidate for PEG rather than nasogastric feeding in order to reduce the risk of pneumonia aspiration while patients with negative MEBDT should undergo FEES and VFSS before starting oral feeding.

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Figure Legends Figure 1. Flow chart of the study Figure 2. Clinical application of new MEBDT

Table 1. Characteristics of study population (n=57) Variables Age (years) Sex (male/female) Cause of Hospitalization  Respiratory Failure  Sepsis  Stroke  Cardiac Injury Timing of performing tracheostomy (days) Timing of mechanical ventilation during tracheostomy (days) Timing of performing swalling test after after being weaned from mechanical ventilation (days) Size of tracheostomy Tracheal cuff pressure (cm H2O)

Number (%) or Mean (SD) 67 ± 5.7 37 (65%) / 20 (35%) 25 (44%) 9 (16%) 3 (5%) 20 (35%) 10 ± 4.5 27 ± 9.8 13 ± 5 7.5 ± 0.7 17±2.7