[Value of blood ammonia on predicting the severity and prognosis of patients with sepsis: a prospective observation study].

OBJECTIVE: To investigate the value of arterial blood ammonia on predicting the severity and prognosis of patients with sepsis. METHODS: A prospective observation study was conducted. A total of 169 patients with sepsis admitted to intensive care unit (ICU) of Jining First People's Hospital Affiliated to Jining Medical University from January 2018 to June 2019 were enrolled. Thirty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score were recorded. At 6-8 hours after the diagnosis of sepsis, the serum levels of arteria blood ammonia and whole blood cell count were run. The septic patients were divided into the sepsis group and septic shock group according to the disease severity, and the septic patients were divided into survival group and death group according to the outcomes during 28-day hospitalization. The clinical data were compared. Spearman rank correlation was applied to determine the correlation between those variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic (ROC) curve. Kaplan-Meier survival curve analysis was used to compare different blood ammonia levels of patients with 28-day cumulative survival rate. RESULTS: Among the 169 sepsis patients, after excluding 12 patients who did not meet the inclusion criteria and loss to follow-up, there were finally 157 patients enrolled in the analysis. Among the 157 septic patients, 71 of them were in the sepsis group, and 86 in the septic shock group. After 28-day follow-up, 115 patients survived and 42 died. No significant differences were found in age and gender among groups with different severity and clinical prognosis. Compared with the control group, the blood ammonia, counts of white blood cell (WBC) and neutrophils ratio (Neut%) in serum of sepsis patients were significantly higher [blood ammonia (µmol/L): 42.28±28.64 vs. 12.05±5.44, WBC (×109/L): 17.51±5.13 vs. 6.57±2.20, Neut%: 0.87 (0.82, 0.90) vs. 0.62 (0.59, 0.67), all P < 0.05]. Compared with the sepsis group, the APACHE II score, blood ammonia, WBC, Neut% and 28-day mortality in the septic shock group were significantly higher [APACHE II score: 24.49±6.22 vs. 14.31±3.32,blood ammonia (µmol/L): 52.93±34.11 vs. 29.38±10.37, WBC (×109/L): 20.21±3.77 vs. 14.02±4.23, Neut%: 0.89 (0.86, 0.92) vs. 0.82 (0.79, 0.89), 28-day mortality: 43.0% (37/86) vs 7.0% (5/71), all P < 0.05]. APACHE II score, blood ammonia, WBC and Neut% in the death group were significantly higher than those in the survival group [APACHE II score: 26.89±7.91 vs. 17.34±4.90, blood ammonia (µmol/L): 69.98±41.14 vs. 32.17±11.31, WBC (×109/L): 20.20±4.78 vs. 16.53±4.91, Neut%: 0.89 (0.87, 0.95) vs. 0.87 (0.82, 0.90), all P < 0.05]. Spearman rank correlation analysis showed that blood ammonia in patients with sepsis was correlated well with APACHE II score (r = 0.592, P < 0.01), and there was moderately positive correlation between blood ammonia and the counts of WBC (r = 0.343, P < 0.01). ROC curve analysis showed that the areas under ROC curve (AUC) of APACHE II score and blood ammonia for predicting 28-day mortality were 0.846 and 0.901, respectively, and there was no statistical significance (P = 0.187). The AUC of APACHE II score combined with blood ammonia was significantly higher than that of APACHE II score alone (0.913 vs. 0.846, P = 0.002), but was not higher than that of blood ammonia alone (0.913 vs. 0.901, P = 0.647). Using a blood ammonia cut-off value of > 36.50 µmol/L for predicting 28-day mortality, the sensitivity and specificity was 92.9% and 73.9%, respectively, and the positive and negative likelihood ratios were 3.56 and 0.10, respectively. Kaplan-Meier survival curve analysis indicated that the patients whose blood ammonia was higher than 36.50 µmol/L, had lower 28-day cumulative survival rate when compared with those patients with blood ammonia ≤ 36.50 µmol/L (Log-Rank test: χ2 = 9.620, P = 0.002). CONCLUSIONS: The level of arterial blood ammonia could somehow indicate the severity and prognosis of sepsis, which could provide evidence for the treatment.

2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside inhibits septic serum­induced inflammatory injury via interfering with the ROS­MAPK­NF­κB signaling pathway in pulmonary aortic endothelial cells.

Sepsis is characterized by injury to the microvasculature and the microvascular endothelial cells, leading to barrier dysfunction. However, the specific role of injury in septic endothelial barrier dysfunction remains to be elucidated. In the present study, it was hypothesized that endothelial cell inflammatory injury is likely required for barrier dysfunction under septic conditions in vitro. 2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside (TSG), a compound extracted from Chinese herbs, is able to inhibit the inflammatory injury of septic­serum in endothelial cells. In the present study, cell viability was assayed by CCK­8 method; mRNA and protein expression was identified by RT­qPCR, western blot or Elisa, respectively and the production of reactive oxygen species was observed by a fluorescence microscope. The present study indicated that septic serum significantly decreased the cell viability of pulmonary aortic endothelial cells (PAECs) following co­cultivation for 6 h, which occurred in a time­dependent manner. TSG notably increased the viability of PAECs in a time­ and concentration­dependent manner. Further investigations revealed that septic serum increased the secretion of interleukin (IL)­1ß, IL­6 and C­reactive protein in PAECs, whereas pretreatment with TSG significantly decreased the secretion of these inflammatory factors. These data indicated that septic serum increased inflammatory injury to the PAECs, and TSG decreased this injury via the reactive oxygen species­mitogen­activated protein kinase­nuclear factor­κB signaling pathway.