Early deep-to-light sedation versus a sustained light-or-awake strategy in mechanically ventilated adults: a target trial emulation
Abstract
Observational studies comparing sedation depth strategies in mechanically ventilated patients have relied on observed consciousness levels alone to define exposure, potentially conflating intentional drug-induced sedation with low arousal caused by residual medications, other agents, or underlying illness. We applied the target trial emulation framework with the clone-censor-weight method to compare early deep-to-light sedation (DTLS) versus a sustained light-or-awake strategy, using a joint exposure definition that requires both Richmond Agitation-Sedation Scale (RASS) depth and qualifying continuous sedative infusion. Using MIMIC-IV (2008–2022), we identified 5,086 adults receiving invasive mechanical ventilation for ≥ 48 h. Each patient was cloned to both strategies. During the primary 144-hour adherence window, inverse probability weights accounted for measured predictors of artificial censoring. The primary outcome was 28-day ventilator-free days (VFDs); successful extubation was analysed with death as a competing event. VFD outcomes were observed before artificial censoring in 1,481 sustained-light-or-awake and 622 DTLS clones. Weighted mean VFDs were 17.72 days for DTLS versus 17.76 days for sustained light-or-awake, a difference of − 0.04 days (95% CI, − 1.32–1.29). The cause-specific extubation HR was 0.97 (95% CI, 0.84–1.11). A sensitivity cohort without future minimum ventilation or ICU-duration requirements ( n = 15,842) showed fewer VFDs with DTLS (difference, − 1.03 days; 95% CI, − 1.47 to − 0.61). These findings do not establish a DTLS benefit; duration-based selection, residual confounding, and limited late-window support constrain interpretation.
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BibTeX
@article{zhang2026early,
title = {{Early deep-to-light sedation versus a sustained light-or-awake strategy in mechanically ventilated adults: a target trial emulation}},
author = {Yuhang Zhang and Menglin Han and Xiaosu Liu and Guanyu Chen and Lulu Zhang},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-75074-2},
url = {https://www.nature.com/articles/s41598-026-75074-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Early deep-to-light sedation versus a sustained light-or-awake strategy in mechanically ventilated adults: a target trial emulation
AU - Yuhang Zhang
AU - Menglin Han
AU - Xiaosu Liu
AU - Guanyu Chen
AU - Lulu Zhang
PY - 2026
DA - 2026/10/15
JO - Scientific Reports
DO - 10.1038/s41598-026-75074-2
UR - https://www.nature.com/articles/s41598-026-75074-2
AB - Observational studies comparing sedation depth strategies in mechanically ventilated patients have relied on observed consciousness levels alone to define exposure, potentially conflating intentional drug-induced sedation with low arousal caused by residual medications, other agents, or underlying illness. We applied the target trial emulation framework with the clone-censor-weight method to compare early deep-to-light sedation (DTLS) versus a sustained light-or-awake strategy, using a joint exposure definition that requires both Richmond Agitation-Sedation Scale (RASS) depth and qualifying continuous sedative infusion. Using MIMIC-IV (2008–2022), we identified 5,086 adults receiving invasive mechanical ventilation for ≥ 48 h. Each patient was cloned to both strategies. During the primary 144-hour adherence window, inverse probability weights accounted for measured predictors of artificial censoring. The primary outcome was 28-day ventilator-free days (VFDs); successful extubation was analysed with death as a competing event. VFD outcomes were observed before artificial censoring in 1,481 sustained-light-or-awake and 622 DTLS clones. Weighted mean VFDs were 17.72 days for DTLS versus 17.76 days for sustained light-or-awake, a difference of − 0.04 days (95% CI, − 1.32–1.29). The cause-specific extubation HR was 0.97 (95% CI, 0.84–1.11). A sensitivity cohort without future minimum ventilation or ICU-duration requirements ( n = 15,842) showed fewer VFDs with DTLS (difference, − 1.03 days; 95% CI, − 1.47 to − 0.61). These findings do not establish a DTLS benefit; duration-based selection, residual confounding, and limited late-window support constrain interpretation.
SN - 2045-2322
ER -