Propofol versus Midazolam With 30-Day Mortality in Sepsis-Associated Acute Kidney Injury: A MIMIC-IV Analysis

Propofol and midazolam are commonly used sedatives in patients with sepsis-associated acute kidney injury (S-AKI), yet the association of their combined use on patient prognosis remains unclear. This study aimed to compare the associations of propofol monotherapy, midazolam monotherapy, and their combination with 30-day mortality in S-AKI patients.

This study analyzed 3335 S-AKI patients from the Medical Information Mart for Intensive Care IV database, categorized by sedation strategy: no sedation, propofol alone, midazolam alone, or combination therapy. The primary outcome was 30-day all-cause mortality. Associations were assessed using Kaplan-Meier survival analysis, Cox proportional hazards models, and inverse probability of treatment weighting. Subgroup and mediation analyses were also performed.

After multivariable adjustment, both midazolam monotherapy (hazard ratio [HR] = 1.945, 95% confidence interval: 1.519-2.490) and combination therapy (HR = 1.573, 95% confidence interval: 1.275-1.942) were associated with significantly increased 30-day mortality risk compared to propofol monotherapy. This finding was consistent after inverse probability of treatment weighting (HR = 1.742 and 1.328, respectively). Subgroup analyses generally supported this trend across different populations. Mediation analysis indicated that metabolic acidosis significantly mediated part of the increased mortality risk associated with midazolam (alone: 15.84%; combined: 10.21%).

Propofol monotherapy was associated with more significant survival benefits compared to midazolam monotherapy or combination therapy. Metabolic acidosis is a key pathological mechanism mediating this difference, which has important guiding value for improving the prognosis of this high-risk population.