Background: Sepsis is a leading cause of death in intensive care units (ICUs), but outcomes of individual patients are difficult to predict. The recently developed clinical metabolomics has been recognized as a promising tool in the clinical practice of critical illness. The objective of this study was to identify the unique metabolic biomarkers and their pathways in the blood of sepsis nonsurvivors and to assess the prognostic value of these pathways. Methods: We searched PubMed, EMBASE, Cochrane, Web of Science, CNKI, Wangfang Data, and CQVIP from inception until July 2019. Eligible studies included the metabolomic analysis of blood samples from sepsis patients with the outcome. The metabolic pathway was assigned to each metabolite biomarker. The meta-analysis was performed using the pooled fold changes, area under the receiver operating characteristic curve (AUROC), and vote-counting of metabolic pathways. We also conducted a prospective cohort metabolomic study to validate the findings of our meta-analysis. Results: The meta-analysis included 21 cohorts reported in 16 studies with 2509 metabolite comparisons in the blood of 1287 individuals. We found highly limited overlap of the reported metabolite biomarkers across studies. However, these metabolites were enriched in several death-related metabolic pathways (DRMPs) including amino acids, mitochondrial metabolism, eicosanoids, and lysophospholipids. Prediction of sepsis death using DRMPs yielded a pooled AUROC of 0.81 (95% CI 0.76-0.87), which was similar to the combined metabolite biomarkers with a merged AUROC of 0.82 (95% CI 0.78-0.86) (P > 0.05). A prospective metabolomic analysis of 188 sepsis patients (134 survivors and 54 nonsurvivors) using the metabolites from DRMPs produced an AUROC of 0.88 (95% CI 0.78-0.97). The sensitivity and specificity for the prediction of sepsis death were 80.4% (95% CI 66.9-89.4%) and 78.8% (95% CI 62.3-89.3%), respectively. Conclusions: DRMP analysis minimizes the discrepancies of results obtained from different metabolomic methods and is more practical than blood metabolite biomarkers for sepsis mortality prediction. Trial registration: The meta-analysis was registered on OSF Registries, and the prospective cohort study was registered on the Chinese Clinical Trial Registry (ChiCTR1800015321).

Objectives: To investigate the clinical value of B-type natriuretic peptide (BNP) in the assessment of severity and prognosis in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Methods: Plasma BNP level, arterial blood gases, serum C-reactive protein level, alveolar-arterial oxygen tension difference and oxygenation index were measured in patients with and without ALI/ ARDS within 24 h of admission to an intensive care unit. Patients with ALI/ARDS were divided into mild, moderate or severe groups according to the degree of hypoxaemia. Survival >28 days was recorded.Results: A total of 59 patients with ALI/ARDS and 14 patients without ALI/ARDS were included in the study. Of the patients with ALI/ARDS, 18 had mild hypoxaemia, 20 had moderate hypoxaemia and 21 had severe hypoxaemia. The mean AE SD BNP level was significantly higher in all three ALI/ ARDS groups (92.41 AE 28.19 pg/ml, 170.64 AE 57.34 pg/ml and 239.06 AE 59.62 pg/ml, respectively, in the mild, moderate and severe groups) than in the non-ALI/ARDS group (47.27 AE 19.63 pg/ml); the increase in BNP level with increasing severity was also statistically significant. When divided according to outcome, the BNP level in the death group (267.07 AE 45.06 pg/ml) was significantly higher than in the survival group (128.99 AE 45.42 pg/ml). Conclusions: The BNP level may be of value in evaluating severity and prognosis in patients with ALI/ARDS.

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