Frontiers in artificial intelligence · 2026
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.
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Qin Guoping, Zou Kun
Аннотация
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.
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.