Early midazolam exposure and short-term risk of acute exacerbation of COPD in critically ill patients: a target trial emulation using the MIMIC-IV database.
- 1Department of Respiratory and Critical Care Medicine, Dongguan Qingxi Hospital, Dongguan, China.
Abstract
Background
Sedation is frequently required in the intensive care unit (ICU), but benzodiazepines may worsen respiratory outcomes in patients with chronic obstructive pulmonary disease (COPD).Objective
To evaluate whether early midazolam exposure after ICU admission is associated with the short-term risk of acute exacerbation of COPD (AECOPD) among critically ill COPD patients.Methods
Using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, we emulated a target trial and applied a clone-censor-weight (CCW) approach to address immortal time bias and informative censoring. Exposure was midazolam administration within a grace period after ICU admission (primary: 24 h; sensitivity: 12 and 36 h). The primary outcome was AECOPD, defined as initiation of systemic corticosteroids or antibiotics between 24 h and 7 days after ICU admission. Outcomes were compared using inverse probability of censoring weights (IPCW).Results
Among 3,416 ICU stays, 233 (6.8%) received midazolam within 24 h. After IPCW weighting, AECOPD incidence was 29.8% in the midazolam group versus 23.5% in controls (risk difference +6.3%, 95% CI -2.7% to +15.8%; odds ratio 1.38, 95% CI 0.86-2.12; p = 0.158). Findings were directionally consistent across grace periods (12 h OR 1.64; 36 h OR 1.29), but none of the grace-period comparisons reached statistical significance.Conclusion
In the primary 24 h analysis, early midazolam exposure was associated with a numerically higher short-term AECOPD risk. These observational findings cannot establish causality, and the present study did not demonstrate a statistically significant causal effect; nevertheless, in view of existing ICU sedation evidence, continued caution in the use of midazolam in critically ill COPD patients appears prudent.
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BibTeX
@article{qin2026early,
title = {{Early midazolam exposure and short-term risk of acute exacerbation of COPD in critically ill patients: a target trial emulation using the MIMIC-IV database.}},
author = {Guoping Qin and Kun Zou},
journal = {Frontiers in artificial intelligence},
year = {2026},
month = oct,
doi = {10.3389/frai.2026.1836581},
url = {https://europepmc.org/article/MED/42903200},
note = {CC BY},
}
RIS
TY - JOUR
TI - Early midazolam exposure and short-term risk of acute exacerbation of COPD in critically ill patients: a target trial emulation using the MIMIC-IV database.
AU - Guoping Qin
AU - Kun Zou
PY - 2026
DA - 2026/10/06
JO - Frontiers in artificial intelligence
DO - 10.3389/frai.2026.1836581
UR - https://europepmc.org/article/MED/42903200
AB - Background Sedation is frequently required in the intensive care unit (ICU), but benzodiazepines may worsen respiratory outcomes in patients with chronic obstructive pulmonary disease (COPD).Objective To evaluate whether early midazolam exposure after ICU admission is associated with the short-term risk of acute exacerbation of COPD (AECOPD) among critically ill COPD patients.Methods Using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, we emulated a target trial and applied a clone-censor-weight (CCW) approach to address immortal time bias and informative censoring. Exposure was midazolam administration within a grace period after ICU admission (primary: 24 h; sensitivity: 12 and 36 h). The primary outcome was AECOPD, defined as initiation of systemic corticosteroids or antibiotics between 24 h and 7 days after ICU admission. Outcomes were compared using inverse probability of censoring weights (IPCW).Results Among 3,416 ICU stays, 233 (6.8%) received midazolam within 24 h. After IPCW weighting, AECOPD incidence was 29.8% in the midazolam group versus 23.5% in controls (risk difference +6.3%, 95% CI -2.7% to +15.8%; odds ratio 1.38, 95% CI 0.86-2.12; p = 0.158). Findings were directionally consistent across grace periods (12 h OR 1.64; 36 h OR 1.29), but none of the grace-period comparisons reached statistical significance.Conclusion In the primary 24 h analysis, early midazolam exposure was associated with a numerically higher short-term AECOPD risk. These observational findings cannot establish causality, and the present study did not demonstrate a statistically significant causal effect; nevertheless, in view of existing ICU sedation evidence, continued caution in the use of midazolam in critically ill COPD patients appears prudent.
SN - 2624-8212
ER -