Integrated comprehensive assessment for predicting weaning success in difficult-to-wean critically ill patients: the WEAN-US study

Liberation from mechanical ventilation (MV) remains challenging, particularly in difficult-to-wean patients. Weaning failure (i.e. inability to wean or post-extubation failure) and spontaneous breathing trial (SBT) failure are often grouped together despite distinct underlying mechanisms. Moreover, most studies have focused on a single physiological predictor of weaning success, although ventilator liberation is a complex, multiorgan process. We hypothesized that a multimodal, ultrasound-based assessment performed during SBT in difficult-to-wean patients would improve prediction of weaning outcomes compared with individual physiological parameters. In this single-center prospective observational study, adult difficult-to-wean patients (≥ 48 h of mechanical ventilation and failure of the first separation attempt) underwent a standardized SBT. A comprehensive assessment of diaphragmatic function, lung aeration, cardiac function, and peripheral muscle strength was performed. In addition, dyspnea assessment and clinical variables were recorded before and at the end of the SBT. An integrated predictive model was developed using clinical selection and Least Absolute Shrinkage and Selection Operator (LASSO) regression, and it was compared with individual predictors. The primary outcome was to predict weaning failure (inability to wean or post-extubation failure). SBT failure was evaluated as a secondary outcome and defined as the inability to successfully complete the SBT due to clinical signs of intolerance. Weaning failure occurred in 27% of patients. Compared with successfully weaned patients, those with weaning failure had lower diaphragmatic contractile reserve (maximal diaphragm thickening fraction), reduced handgrip strength, higher prevalence of ICU-acquired weakness, greater dyspnea after SBT, and more pronounced loss of lung aeration during SBT. Cardiac parameters, including higher ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e’) and ejection fraction, were associated with SBT failure, whereas neuromuscular impairment was more strongly associated with post-extubation failure. An integrated model demonstrated good predictive performance (AUROC 0.88; 95% CI 0.78–0.95), outperforming individual predictors in predicting weaning failure. In difficult-to-wean patients, SBT failure and weaning failure are driven by several interacting physiological mechanisms. A multimodal, ultrasound-based approach integrating cardiac, pulmonary, diaphragmatic, and neuromuscular domains improves prediction of weaning outcomes and may enable more individualized ventilator liberation strategies. This study was prospectively registered in clinicaltrial.gov (NCT05539599; First Posted 2022–09-14).