Effect of ß-blockers on mortality in patients with sepsis: A propensity-score matched analysis.

Objectives: We aimed to evaluate the association between ß-blocker therapy and mortality in patients with sepsis. Methods: Patients with sepsis were selected from the Medical Information Mart for Intensive Care (MIMIC)-III. Propensity score matching (PSM) was used to balance the baseline differences. A multivariate Cox regression model was used to assess the relationship between ß-blocker therapy and mortality. The primary outcome was the 28-day mortality. Results: A total of 12,360 patients were included in the study, involving 3,895 who received ß-blocker therapy and 8,465 who did not. After PSM, 3,891 pairs of patients were matched. The results showed that ß-blockers were associated with improved 28- (hazards ratio (HR) 0.78) and 90-day (HR 0.84) mortality. Long-acting ß-blockers were associated with improved 28-day survival (757/3627 [20.9%] vs. 583/3627 [16.1%], P < 0.001, HR0.76) and 90-day survival (1065/3627 [29.4%] vs.921/3627 [25.4%], P < 0.001, HR 0.77). Short-acting ß-blocker treatment did not reduce the 28-day and 90-day mortality (61/264 [23.1%] vs. 63/264 [23.9%], P = 0.89 and 83/264 [31.4%] vs. 89/264 [31.7%], P = 0.8, respectively). Conclusions: ß-blockers were associated with improved 28- and 90-day mortality in patients with sepsis and septic shock. Long-acting ß-blocker therapy may have a protective role in patients with sepsis, reducing the 28-day and 90-day mortality. However, short-acting ß-blocker (esmolol) treatment did not reduce the mortality in sepsis.

Hippocampus-prefrontal cortex inputs modulate spatial learning and memory in a mouse model of sepsis induced by cecal ligation puncture.

AIMS: Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments. However, the pathophysiology of SAE is complex and unclear. Here, we investigated the role of hippocampus (HPC)-prefrontal cortex (PFC) in cognitive dysfunction in sepsis induced by cecal ligation puncture (CLP) in mice. METHODS: The neural projections from the HPC to PFC were first identified via retrograde tracing and viral expression. Chemogenetic activation of the HPC-PFC pathway was shown via immunofluorescent staining of c-Fos-positive neurons in PFC. Morris Water Maze (MWM) and Barnes maze (BM) were used to evaluate cognitive function. Western blotting analysis was used to determine the expression of glutamate receptors and related molecules in PFC and HPC. RESULTS: Chemogenetic activation of the HPC-PFC pathway enhanced cognitive dysfunction in CLP-induced septic mice. Glutamate receptors mediated the effects of HPC-PFC pathway activation in CLP mice. The activation of the HPC-PFC pathway resulted in significantly increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, pCREB, and BDNF in PFC. However, inhibition of glutamate receptors using 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)quinoxaline (NBQX), which is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR inhibitor), or D-2-amino-5-phosphonopentanoate (D-AP5), which is an NMDA receptor antagonist abolished this increase. CONCLUSION: Our study reveals the important role of the HPC-PFC pathway in improving cognitive dysfunction in a mouse model of CLP sepsis and provides a novel pathogenetic mechanism for SAE.