(A-114) Effects of Different Sedation Regimens on Mortality in Post-Cardiac Surgery Patients: A Target Trial Emulation Study

Background: Sedation management in critically ill post-cardiac surgery patients is crucial, yet the impact of different sedation regimens on mortality remains uncertain. Randomized controlled trials (RCTs) are often impractical due to ethical and logistical constraints, making real-world data (RWD) a valuable alternative for evaluating clinical interventions. This study leverages electronic health records (EHR) to emulate a target trial comparing sedation strategies and their effects on long-term mortality.

Objectives: To assess the impact of propofol alone versus propofol combined with dexmedetomidine or midazolam on 28-day, 90-day, and 180-day mortality in post-cardiac surgery patients admitted to the intensive care unit (ICU).

Methods: Using a target trial emulation (TTE) approach, we analyzed data from MIMIC-IV (v3.1), a large deidentified critical care dataset from Beth Israel Deaconess Medical Center (BIDMC). Patients aged ≥18 who underwent cardiac surgery and received sedation within 24 hours of ICU admission were included. Exclusion criteria included ICU stays < 48 hours and missing mortality data. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for baseline confounders. The primary outcome was mortality at 28, 90, and 180 days. Secondary outcomes included ventilator-free and vasopressor-free days, ICU length of stay, and maximum norepinephrine dose.

Results: Among 4,913 eligible patients, 3,351 received propofol alone, 1,225 received propofol-dexmedetomidine, and 337 received propofol-midazolam.
Propofol-dexmedetomidine was associated with significantly lower 28-day mortality (HR = 0.69, 95% CI 0.55–0.86, p < 0.01), with consistent benefits at 90 and 180 days.
Propofol-midazolam was associated with significantly higher 28-day mortality (HR = 5.47, 95% CI 3.60–8.32, p < 0.001), as well as increased norepinephrine use (2.9 vs. 1.6 mg/min, p < 0.001), longer vasopressor dependence (23.8 vs. 20.3 days, p < 0.001), and prolonged mechanical ventilation (21.2 vs. 17.6 days, p < 0.01).

Conclusions: This study demonstrates the potential of real-world evidence (RWE) from EHR-based databases in guiding sedation strategies in ICU settings. Propofol-dexmedetomidine is associated with improved survival, while propofol-midazolam is linked to increased mortality and prolonged ICU interventions. Given the challenges of conducting RCTs in ICU sedation, real-world studies using advanced analytical frameworks, such as TTE, are essential for informing regulatory and clinical decision-making. Further research is needed to optimize sedation protocols for post-cardiac surgery patients.