Hemodynamic Effects of Guideline-Based Sedation in Mechanically Ventilated Adults: A Multicenter Observational Analysis

Propofol is a first-line sedative for adults receiving invasive mechanical ventilation (IMV). However, it can contribute to hemodynamic instability, especially during intubation. The magnitude, timing, risk factors, and variability of sedation-associated mean arterial pressure (MAP) changes remain poorly characterized in ICU settings. To quantify MAP changes following propofol sedation, identify risk factors for hemodynamic instability, and characterize associated interventions. Retrospective cohort study. The primary outcome was MAP change within 2 hours following sedation. Secondary outcomes included vasopressor use and hypotension (MAP ≤ 60 mm Hg). Mixed-effects modeling was used to account for individual patient differences. Adults (≥ 18 yrs old) who required IMV and received greater than or equal to 6 consecutive hours of propofol infusion, between May 5th, 2018, and July 31st, 2024, in 11 ICUs across the Mayo Clinic, spanning 5 hospitals in 4 states. The primary outcome was the change in MAP within 2 hours following the initiation of propofol-based sedation. Across 16,418 patients, 25.2% were on vasopressors before sedation initiation. Among the remaining 12,281 patients, 40.3% required vasopressors and 7.7% experienced hypotension within 2 hours of sedation. Propofol-based sedation was associated with a MAP reduction within the first 30 minutes (-6.58 mm Hg; 95% CI, -6.85 to -6.32; p < 0.001). There was substantial interpatient variability in both baseline MAP, and MAP decline after sedation (9.5 and 40.9% between-patient differences, respectively). Higher Sequential Organ Failure Assessment (SOFA) scores (-0.31 mm Hg/point), older age (-0.04 mm Hg/yr), and male sex (-0.47 mm Hg) were associated with lower MAP. Patients with higher illness severity experienced progressively greater MAP decline over time (-0.20 mm Hg/hr/SOFA point; p < 0.001). Propofol-based sedation was associated with clinically significant hemodynamic effects requiring intervention in the early post-intubation period. The marked interpatient variability in hemodynamic responses highlights the importance of personalized management approaches, including risk stratification based on age, sex, and illness severity.