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.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.