Early Versus Deferred De-escalation From Controlled Ventilation After a 48-Hour Landmark of Physiological Stability

Background: Mechanical ventilation is life-saving, yet optimal timing of transition from controlled to assisted modes remains uncertain. Prolonged controlled ventilation exposes patients to sedation, diaphragm dysfunction, and lung injury, while premature de-escalation risks asynchrony and reintubation.

Design: Landmark target trial emulation with 48-hour eligibility ascertainment.

Eligibility: Adults ≥18 years, invasive mechanical ventilation >24 hours, alive and ventilated at 48 hours with classifiable Day-2 mode (controlled or assisted), Day-2 FiO₂ ≤50%, Day-2 PEEP ≤10 cmH₂O.

Strategies: Early-support level decreased by Day 3 (mode step-down from controlled to assisted, or successful extubation while alive); Deferred-support maintained or increased.

Analysis: Single-interval CCW estimator with stabilised IPCW (truncated 1st-99th percentile), propensity model with 21 baseline covariates, bootstrap 95% CIs (2,000 resamples primary; 800 sensitivity). Sensitivity analyses: no truncation, ICU mortality, unweighted per-protocol, extended 40-covariate adjustment, 5th-95th truncation, AIPW doubly robust estimator. E-values computed for unmeasured confounding.

External validation: Harmonised protocol in eICU-CRD v2.0 (208 hospitals, n=10,957), outcome: in-hospital mortality.

Inclusion criteria

• Age ≥18 years
• Invasive mechanical ventilation for >24 hours
• Alive and still ventilated at 48 hours after ICU admission
• Classifiable Day-2 ventilatory mode (controlled or assisted/spontaneous)
• Day-2 FiO₂ ≤50%
• Day-2 PEEP ≤10 cmH₂O

Exclusion criteria

• Death during the 24-hour grace period (Day 2 to Day 3)
• Unascertainable Day-3 strategy (missing mode without documented ventilation end)