Trans-cuff budesonide delivery and its effects on endotracheal intubation-induced subglottic injury

Abstract

Objectives This study aimed to determine whether budesonide inhalation suspension (BIS) diffuses through polyvinyl chloride (PVC) endotracheal tube (ETT) cuffs and whether intracuff budesonide attenuates the acute subglottic injury during endotracheal intubation (ETI) in a rabbit model. Methods in vitro , high-performance liquid chromatography was used to quantify trans-cuff diffusion of budesonide from 2.5-mm-ID PVC ETT cuffs. For the in vivo study, 32 New Zealand White rabbits were allocated to four groups ( n =8): control (Con), air-inflated cuff (Air), normal saline-inflated cuff (NS), and BIS-inflated cuff (Bud). Intubated rabbits underwent 12 h of ETI at an intracuff pressure of 22 mmHg. Subglottic tissues were harvested immediately after extubation for histological and immunofluorescence analyses. Results Budesonide diffusion across PVC ETT cuffs was temperature-dependent during the first 12 h and continued at 37°C for at least 14 days. In vivo , all ETI groups developed acute subglottic histological injury. Compared with the Air and NS groups, the Bud group had lower IL-1β, IL-6, and TNF-α fluorescence intensities ( P < 0.05), whereas the measured histological outcomes and CD86/CD206 levels did not differ significantly among the ETI groups. No significant differences were observed between the Air and NS groups. Conclusions Budesonide diffuses across PVC ETT cuffs, and intracuff BIS was associated with lower subglottic IL-1β, IL-6, and TNF-α fluorescence intensities during a 12-hour acute ETI model. The findings do not establish prevention of histological injury and require confirmation in longer-duration pharmacokinetic and outcome studies.