Water-soluble contrast agent during swallowing study increases aspiration sensitivity and antedates oral feeding without respiratory and drug complications: a prospective, observational, case-control Trial v1

Water-soluble contrast agent during swallowing study increases aspiration sensitivity and antedates oral feeding without respiratory and drug complications: a prospective, observational, case-control Trial Project summary In traditional video-fluoroscopic-swallowing study, a lipid-soluble contrast (barium sulfate) has been used more than 30 years. However, it can cause chemical pneumonitis and subsequently impair reliability of video-fluoroscopic swallowing study if aspirated. The authors reviewed the safety and usefulness of a water-soluble agent-based swallowing test. General information Protocol title, protocol identifying number (if any), and date. Brief Title: Feasibility of a Water-soluble Contrast Application Into Dysphagia Evaluation Official Title: Feasibility of a Water-soluble Contrast Application Into Dysphagia Evaluation ClinicalTrials.gov ID: NCT03598491 (13/07/2015) Name and address of the sponsor/funder. Sponsor: Ulsan University Hospital Funder: National Research Foundation of Korea grant (NRF-2017R1A2B4011478) Name and title of the investigator(s) who is (are) responsible for conducting the research, and the address and telephone number(s) of the research site(s), including responsibilities of each. Responsible Party: Principal Investigator Investigator: Chang Ho Hwang Official Title: Tenured Professor, PhD and MD Affiliation: Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwando-ro, Dong-gu, Ulsan 44033, Republic of Korea Tel: + 82-52-250-7210, Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or institutions involved in the research Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwando-ro, Dong-gu, Ulsan 44033, Republic of Korea Rationale & background information Aspiration pneumonia prolongs hospital stay and increases medical comorbidities and social costs. In most patients, aspiration pneumonia starts as non-infectious repetitive micro-aspirations. Although the most important risk factor for aspiration pneumonia is swallowing dysfunction, many patients do not present with this condition until pneumonia is established. Although the modified barium swallowing study (MBSS) is considered the gold standard for assessing aspiration risk, aspiration of lipid-soluble barium can cause chemical pneumonitis or impair radiologic interpretation of the lungs. Water soluble contrast agents (WSCAs) may avoid these complications while maintaining sensitivity on aspiration. References (of literature cited in preceding sections) 1.DiBardino DM, Wunderink RG: Aspiration pneumonia: a review of modern trends. Journal of critical care 30: 40-48, 2015. 2.Kendall KA: Evaluation of airway protection: Quantitative timing measures versus penetration/aspiration score. The Laryngoscope 127: 2314-2318, 2017. 3.Purkey MT, Levine MS, Prendes B, Norman MF, Mirza N: Predictors of aspiration pneumonia following radiotherapy for head and neck cancer. The Annals of otology, rhinology, and laryngology 118: 811-816, 2009. 4.Martin-Harris B, Brodsky MB, Michel Y, Castell DO, Schleicher M, Sandidge J, Maxwell R, Blair J: MBS measurement tool for swallow impairment--MBSImp: establishing a standard. Dysphagia 23: 392-405, 2008. 5.Kuhlemeier KV, Yates P, Palmer JB: Intra- and interrater variation in the evaluation of videofluorographic swallowing studies. Dysphagia 13: 142-147, 1998. 6.Lareau DG, Berta JW: Fatal aspiration of thick barium. Radiology 120: 317, 1976. 7.Franquet T, Gimenez A, Roson N, Torrubia S, Sabate JM, Perez C: Aspiration diseases: findings, pitfalls, and differential diagnosis. Radiographics 20: 673-685, 2000. 8.Harris JA, Bartelt D, Campion M, Gayler BW, Jones B, Hayes A, Haynos J, Herbick S, Kling T, Lingaraj A, Singer M, Starmer H, Smith C, Webster K: The use of low-osmolar water-soluble contrast in videofluoroscopic swallowing exams. Dysphagia 28: 520-527, 2013. 9.Tamm I, Kortsik C: Severe barium sulfate aspirationinto the lung: clinical presentation, prognosis and therapy. Respiration; international review of thoracic diseases 66: 81-84, 1999. 10.Voloudaki A, Ergazakis N, Gourtsoyiannis N: Late changes in barium sulfate aspiration: HRCT features. European radiology 13: 2226-2229, 2003. Study goals and objectives Although the modified barium swallowing study (MBSS) is considered the gold standard for assessing aspiration risk, aspiration of lipid-soluble barium can cause chemical pneumonitis or impair radiologic interpretation of the lungs. Water soluble contrast agents (WSCAs) may avoid these complications while maintaining sensitivity on aspiration. It was conducted for confirmation of the safety and usefulness of a water-soluble agent-based swallowing test. Study Design Study Type: Observational Observational Study Model: Cohort Time Perspective: Prospective Biospecimen Retention: None Retained Biospecimen Description: Enrollment: 755 [Actual] Number of Groups/Cohorts: 2 Detailed Description; Parallel-group, case-controlled trial was conducted from September 2015 to November 2017. All the patients who referred for video-fluoroscopic-swallowing study were screened. Based on the pre-emptive evaluation, high-risky patients were allocated to iohexol (Omnipaque)-used video-fluoroscopic-swallowing study and others were allocated to barium sulfate-used video-fluoroscopic-swallowing study. Statistical Package for the Social Sciences 24 was used to perform statistical analysis for the data. Quantitative data were presented as mean ± standard errors. Methodology Conditions Dysphagia, Swallowing Disorder Eligibility Study Population: All the inpatients and outpatients who referred for video-fluoroscopic-swallowing study Sampling Method: Non-Probability Sample Minimum Age: > 3yr Maximum Age: No Sex: All Gender Based: No Accepts Healthy Volunteers: No Inclusion Criteria: • All the patients who referred for video-fluoroscopic-swallowing study Exclusion Criteria: • none Based on their medical conditions and aspiration risk, patients undergoing the swallowing study were assigned to iohexol 350 (Omnipaque® [osmolarity 541 mOsm/L, viscosity 10.4 centipoise at 37°C, specific gravity of 1.406], GE Healthcare, USA)(19) or barium sulfate (BaSO4 40% [osmolarity 233 mOsm/L, viscosity 2.3 centipoise at 25°C]) as the CA. Patients with a history of iodine allergy underwent MBSS. The demographic and clinical characteristics of all patients were collected, including underlying diseases, performance of tracheostomy, feeding methods, radiologic findings before and after the swallowing study, total hospital stay, and days to discharge. Based on the penetration-aspiration scale, aspiration was defined as CA passing below the vocal folds. Patients were asked to sit in a wheel-chair with neutral neck, erect trunk, hips and knees flexed to 90 degrees, and feet in contact with the floor. Patients were allowed to grip a safety bar, or assistants held their trunk, if necessary. Patients were assessed in lateral and/or anterior-posterior view using a fluoroscope (Shimavision 3500 HG, Shimadzu, South Korea). MBSS was performed according to the modified Logemann protocol; nectar-thick liquid was first evaluated and pureed, yielding semi-solid and solid test diets, and finally juice-thick liquid. WSS was performed using Hwang’s protocol, consisting of juice-thick liquid and then pureed, semi-solid and solid diets. The amount of each material depended on the results of preceding analyses. Safety Considerations Based on their medical conditions and aspiration risk, type of the swallowing study was chosen. If present, Levin tubes were removed > 4 hours before the evaluations and oxygen was provided during the swallowing study, as requested. Results suggesting pneumonitis, pulmonary edema, allergic responses, or chemotoxicity-related laboratory/vital findings were collected over 1 week after the evaluations. Follow-Up Primary Outcome Measure: 1. Laryngeal protection Penetration aspiration scale (zero to eight) [Time Frame: within 1 hour after video-fluoroscopic-swallowing study] Secondary Outcome Measure: 2. Oral feeding Success of Oral feeding after video-fluoroscopic-swallowing study or not [Time Frame: within 1 week before video-fluoroscopic-swallowing study] Other Pre-specified Outcome Measures: 3. Tracheostomy Presence of tracheostomy or not [Time Frame: within 1 day before video-fluoroscopic-swallowing study] 4. Allergic reaction Contrast allergic reaction to the Iohexl [Time Frame: within 2 days before video-fluoroscopic-swallowing study] 5. Symptoms of chemical pneumonitis Radiological alteration on a chest xray [Time Frame: within 1 week before video-fluoroscopic-swallowing study] 6. Hospital stay Total days from admission to discharge [Time Frame: within 1 day after discharge] 7. Days to discharge Total Days from video-fluoroscopic-swallowing study to discharge [Time Frame: within 1 day after discharge] Data Management and Statistical Analysis Normal distribution, skewness, and kurtosis were assessed using the Shapiro-Wilk or Kolmogorov-Smirnov test, and non-normally distributed variables were log-transformed. Parameters in the MBSS and WSS groups were compared by the Chi-square test, Fisher's exact test, or two sample independent t-tests, as appropriate. The amounts of swallowed and aspirated CA were compared with radiologic change or aggravation within each group by Spearman correlation analysis. Demographic data were analyzed by two-sample independent t-tests or Fisher's exact tests, as appropriate. All statistical analyses were performed using Statistical Package for the Social Sciences 24 software, with p < 0.05 considered statistically significant. Quality Assurance All patients were evaluated by a physiatrist with an intra-rater reliability of oropharyngeal swallowing efficiency of 0.87. Data Monitoring: Yes; Board Name: Ulsan University Hospital Institutional Review Board Expected Outcomes of the Study A WSCA would show a similar diagnostic accuracy for dysphagia, compared with barium. A WSCA would have sufficient solubility in water and low osmolarity to avoid aspiration-induced chemical/hyperosmolar reactions and sufficient radio-opacity to detect aspiration. Dissemination of Results and Publication Policy The protocol will be specified not only dissemination of results in the scientific media, but also to the community and/ or the participants, and consider dissemination to the policy makers where relevant. Duration of the Project Overall Status: Completed Study Start: September 18, 2015 [Actual] Primary Completion: November 17, 2017 [Actual] Study Completion: December 31, 2017 [Actual] Problems Anticipated Because of an observation trial, the difficulties that we anticipated in successfully completing our projects within the time frame stipulated and the funding requested did not happened. Project Management Chang Ho Hwang: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing – original draft, writing – review and editing Baek Hee Jang: Conceptualization, data curation, investigation, methodology, project administration, resources, software, writing – original draft, writing – review and editing Eun Ji Park: statistical analysis Mun Seulah and Na-Young Joo: spreadsheets Ethics Research involving human participants and/or animals: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent Forms Informed consent was obtained from all individual participants included in the study. Budget Financial/nonfinancial disclosures This work was supported the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science, ICT & Future Planning) (NRF-2017R1A2B4011478). Chang Ho Hwang takes responsibility for the National Research Foundation of Korea grant (NRF-2017R1A2B4011478). Other support for the Project No funding received or anticipated for this project from other funding organizations. Collaboration with other scientists or research institutions No collaboration with other scientists or research institutions Links to other projects No links to other projects