Randomized Trial of Corticosteroids for Post-Extubation Aspiration

PROJECT SUMMARY/ABSTRACT Dysphagia and aspiration are significant health problems associated with aging. By 2030, the United States elderly population is anticipated to exceed 72 million, with over 12 million of these individuals experiencing swallowing dysfunction. In the over 1,000,000 acute respiratory failure (ARF) patients each year who require

mechanical ventilation, one common cause of prolonged swallowing dysfunction is injury from the endotracheal tube. Occurring in as many as 44% of these ARF survivors, post-extubation aspiration is associated with deleterious consequences including pneumonia, percutaneous feeding tube placement, long term care facility

admission, and increased hospital mortality. These complications of aspiration must be weighed against delaying the resumption of oral feeding that is associated with prolonged enteral tube feeding, increased caregiver burden, patient dissatisfaction, and increased health-related costs. As our population ages, elderly

ARF survivors are growing in number, and are at increased risk for post-extubation dysphagia and aspiration. The only current treatment options are to modify the dietary texture and/or place enteral feeding tubes while waiting weeks to months for the dysphagia to resolve. In our previous R21 cohort of 213 ARF survivors, we

identified that at the time of extubation, laryngeal edema was present in 56% of ARF survivors and associated with a 3-fold risk of aspiration. Corticosteroids may reduce this inflammatory laryngeal edema. Clinical trials and meta-analyses have demonstrated that peri-extubation intravenous corticosteroids reduce the need for

reintubation, raising the possibility that corticosteroids work through reducing the laryngeal edema. We hypothesize that a similar dosing regimen of a short course of intravenous corticosteroids could restore normal laryngeal swallowing function, improve post-extubation dysphagia, and reduce susceptibility of aspiration. This

proposal will continue to utilize our established multi-center research group at Colorado, Boston University, Stanford, and Yale. We have worked together as a collaborative research group for nearly ten years. With our current R01 infrastructure, we will conduct a multi-center randomized trial of corticosteroids for ARF survivors

with documented post-extubation laryngeal edema. The patients with laryngeal edema on their post extubation FEES examination (performed as part of the R01 protocol) will be randomized to 24 hours of intravenous corticosteroids or an equivalent placebo, and then undergo a repeat FEES examination within 48 hours of the

last study dose. Our primary mechanistic outcome will be improvement in laryngeal edema using the revised Patterson edema scale, with secondary in hospital outcomes of improved swallowing function and reduction in aspiration. We will also follow participants after hospital discharge to determine whether corticosteroids

improve quality life including enhanced swallowing function and return to their pre-hospitalization diet. The results of this R21 proposal will help develop the first personalized therapy for post-extubation dysphagia, a common disorder in our aging population.