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
Year: 2026
Type: article
Study design: Observational Study
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: = 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.
Authors: Guoping Qin, Kun Zou
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,353
OpenAlex ID: W7220741419