Distinct weaning phenotypes in patients unsuccessful in weaning from invasive mechanical ventilation: a secondary analysis of the WEAN SAFE cohort

Objective: To characterise the trajectories and outcomes of patients who enter the weaning process but fail to wean from invasive mechanical ventilation (MV). Methods: In this secondary analysis of the WorldwidE AssessmeNt of Separation of pAtients From ventilatory assistancE (WEAN SAFE) cohort, we examined weaning duration and intensity, decisions to withdraw or withhold life-sustaining therapy (WLST), and clinical outcomes in patients not weaning from invasive ventilation. The primary outcome was ICU mortality. Results: Of the 5664 patients in the study population, 1270 (22.4%) never underwent a separation attempt (SA), while 4394 (77.6%) had at least one SA; of these, 664 (15.1%) eventually failed weaning from invasive MV at day 90, while 3730 (65.9%) successfully weaned. Failed-Wean patients had the longest duration of invasive ventilation and longest ICU stay of all groups. Compared with Successful-Wean, Failed-Wean patients underwent more separation attempts, but fewer attempted extubations and more reintubations and tracheostomies. ICU mortality was 78% in Failed-Wean compared with 2% in Successful-Wean. Three clinically distinct Failed-Wean phenotypes were identified, distinguished by separation attempt count and WLST timing: Phenotype A (single SA + WLST), Phenotype B (single SA, no WLST), and Phenotype C (> 1 SA). A failed-first SA was strongly associated with WLST decisions. In this cohort, a WLST decision was associated with a higher hazard of ICU mortality and shorter median time to ICU death. Conclusions: Three weaning failure phenotypes were identified with distinct clinical profiles, weaning trajectories, and outcomes. A strong relationship exists between failed first separation attempts, WLST decision, and the risk of death, which deserves further investigation. Trial registration: ClinicalTrials.gov, NCT03255109.