Abstract
Objective
Mechanically ventilated sepsis patients have a high mortality rate. This retrospective cohort study aimed to investigate the impact of dexmedetomidine on the clinical prognosis of mechanically ventilated sepsis patients and to analyze its correlation with local pulmonary inflammation and oxidative stress status.
Methods
Patients admitted between January 2022 and December 2025 who met the Sepsis 3.0 diagnostic criteria and received invasive mechanical ventilation for over 24 h were included. Based on whether dexmedetomidine was administered within 72 h of sepsis diagnosis, patients were divided into a dexmedetomidine-exposed group (DEX group) and a non-exposed group (Non-DEX group). The primary outcome was 28-day mortality risk. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and total hospital stay. By measuring levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD) in bronchoalveolar lavage fluid (BALF), the local pulmonary inflammatory and oxidative stress status were assessed. Kaplan-Meier survival curves, multivariable Cox regression models, and other methods were used to analyze the association between dexmedetomidine exposure and clinical outcomes, as well as local pulmonary inflammation and oxidative stress status.
Results
A total of 168 patients were included (58 in the DEX group, 110 in the Non-DEX group), with an overall 28-day mortality rate of 57.14% (51.72% in DEX group vs 69.09% in Non-DEX group). The median survival time was 31 days in the Dex group and 23 days in the Non-Dex group. The death risk in the Non-Dex group was 1.627 times that of the Dex group. After adjusting for confounding factors such as baseline Sequential Organ Failure Assessment (SOFA) score, shock status, and blood lactate level, dexmedetomidine use was independently associated with a reduced 28-day mortality risk (Hazard Ratio [HR] = 0.65, 95% CI: 0.46-0.79, P = 0.00362). There was no significant difference in mechanical ventilation time between the two groups (P = 0.2217), but the DEX group had longer ICU and total hospital stays (P = 0.015, 0.0484, respectively). Analysis of BALF samples showed that TNF-α, IL-6, and MDA levels were significantly lower, while SOD activity was significantly higher in the DEX group (all P < 0.05).
Conclusion
In mechanically ventilated sepsis patients, dexmedetomidine exposure was independently associated with reduced 28-day mortality risk. The survival benefit may be related to the alleviation of local pulmonary inflammation and oxidative stress, with improvements in BALF biomarkers providing direct evidence. The study suggests that dexmedetomidine may have a dual role of sedation and potential organ protection for the high-risk population.
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