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Sivelestat Improves Clinical Outcomes and Decreases Ventilator-associated Lung Injury in Children with Acute Respiratory Distress Syndrome: a Retrospective Cohort Study

Overview
Journal Transl Pediatr
Specialty Pediatrics
Date 2022 Nov 8
PMID 36345446
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Abstract

Background: Sivelestat, a neutrophil elastase inhibitor, is a selective and targeted therapy for acute respiratory distress syndrome (ARDS) in adults; and it is also reported to apply to children with ARDS. However, there is little evidence of its efficacy in children.

Methods: This study recruited 212 patients ranging in age from 28 days to 18 years old, and who met the diagnostic criteria for pediatric ARDS (PARDS) while hospitalized in the Intensive Care Department of the Affiliated Children's Hospital of Xi'an Jiaotong University. A total of 125 patients (case group) received sivelestat treatment, and 87 were assigned to the control group. There were no significant differences in gender (P=0.445) or age (P=0.521). Control group data were collected from the Electronic Case Information System for pediatric patients diagnosed with ARDS between March 2017 to January 2020. Data for the case group were collected from the Electronic Case Information System between February 2020 to February 2022. Demographic data, clinically relevant indicators, respiratory parameters were recorded. The 28-day mortality was the primary endpoint; the Kaplan-Meier and log-rank tests were used to evaluate cumulative survival rate.

Results: For general demographic and clinical characteristics, no significant differences were observed between the two groups. Compared to the control group, the case group displayed significant improvements in PaO/FiO at 48 h (141±45 115±21, P<0.001) and 72 h (169±61 139±40, P<0.001) post-admission, and plateau pressure was lower than that in the control group at 24 h (24±3 . 28±7, P<0.001), 48 h (21±4 . 26±7, P<0.001), and 72 h (20±2 . 25±6, P<0.001) post-admission. Interleukin-8 levels were lower in the case group at 48 and 72 h post-admission. Overall, 28-day mortality was 25.47% (54/212). Twenty-five children died in the sivelestat group, 29 children died in the control group. Survival analysis revealed that cumulative survival in the case group was higher than that in the control group (P=0.028).

Conclusions: ARDS is expected to have high morbidity and mortality in critical care medicine, and precise targeted drugs are lacking. Our study showed that sivelestat improved prognosis and reduces mortality in children with ARDS.

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Sivelestat sodium alleviated sepsis-induced acute lung injury by inhibiting TGF-β/Smad signaling pathways through upregulating microRNA-744-5p.

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