敗血症患者におけるデクスメデトミジンの腸内細菌叢調節と長期生存率改善：傾向スコアマッチング解析
Yisen Zeng1, Huiling Wu1, Huaijian Zhang2
1Intensive Care Unit, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China.
Background:
The interplay between sedative agents and the gut microbiome may influence long-term outcomes in sepsis, but data are scarce. This study compared the effects of dexmedetomidine vs. propofol sedation on long-term survival in mechanically ventilated sepsis adults, with an exploratory focus on the gut microbiome and pre-existing malignancies.
Methods:
In this multicenter, retrospective cohort study, 1,295 mechanically ventilated adults with sepsis (2013-2020) were analyzed. Propensity score matching (1:1) balanced 27 baseline covariates, producing 177 matched pairs. Primary outcomes were 30-day, 90-day, and 5-year mortality. Secondary outcomes included delirium/coma-free days, cardiovascular safety, and 6-month functional status. Subgroup analyses assessed pre-existing malignancies and high antibiotic exposure (≥7 days before enrollment) as proxies for microbiome disruption. Gut microbiota composition was characterized via 16S rRNA sequencing in a pre-specified subcohort (n = 89).
Results:
After matching, dexmedetomidine was associated with significantly lower 5-year mortality (34.5% vs. 45.2%; HR 0.64, 95% CI 0.52-0.79; p = 0.039). Survival curves progressively diverged beyond 180 days. No differences were observed in short-term neurological outcomes or cardiovascular safety. Subgroup analyses showed enhanced survival benefits with dexmedetomidine in patients aged >65, females, those with pulmonary-source sepsis, SOFA >10, baseline delirium, pre-existing malignancies (OR 2.10, 95% CI 1.15-3.85; p = 0.015), and high antibiotic exposure as a proxy for gut dysbiosis (OR 1.95, 95% CI 1.08-3.52; p = 0.028). Exploratory 16S rRNA analysis in a subset (n = 89) revealed that dexmedetomidine was associated with enriched beneficial genera such as Faecalibacterium and Bifidobacterium, while propofol correlated with increased Enterococcusand Escherichia/Shigella.
Conclusions:
Dexmedetomidine sedation is associated with a significant 5-year survival benefit in mechanically ventilated sepsis patients, particularly among those with malignancies or factors predisposing to gut dysbiosis. The observed modulation of the gut microbiome toward a more symbiotic state provides a plausible mechanistic insight into these clinical findings, highlighting a potential role for microbiota-centric strategies in critical care.
