Impact of mobilization dose on outcome of critically ill patients receiving mechanical ventilation—a target trial emulation using data from the TEAM trial

RATIONALE: Variability in the outcomes of mobilization interventions is expected due to their complexity, and one of the post hoc hypotheses for the findings of the TEAM trial is the impact of "dosage" of mobilization on clinical outcomes. OBJECTIVES: The aim of the present study is to understand the impact of the "dose" of mobilization on 28-day mortality of patients included in the TEAM trial. METHODS: A target trial emulation estimating the per-protocol effect, which is the effect had all patients in the trial adhered to strategies with different "doses" and timing, was used. All patients included in the TEAM trial (adults in the intensive care unit [ICU] who were undergoing invasive mechanical ventilation) were included and the primary outcome was 28-day mortality. Simulated interventions combining different thresholds of duration of mobilization and different thresholds of highest ICU Mobility Scale (IMS) achieved in each day were assessed using g-formulas considering baseline and time-varying confounders. MEASUREMENTS AND MAIN RESULTS: Overall, 741 patients were included, with a median age of 62 (IQR, 51-71) years; 37% were female. Prolonged mobilization time carried worse outcomes when lower levels of mobility were achieved (risk ratio [RR], 1.33 [95% CI, 1.10-1.63] for mobilization time ≤20 minutes and mobility scale of 2). When an IMS >4 was achieved on a given day, prolonged duration of mobilization did not increase mortality compared to natural course (RR, 1.13 [95% CI, 0.96-1.46] for mobilization time ≤20 minutes and IMS of 4). CONCLUSIONS: Prolonged mobilization when only lower IMS levels could be achieved was associated with increased 28-day mortality.