Abstract

Background. Previous studies assessing various cytokines in the critically ill/injured have been uninformative in terms of translating to clinical care management. Animal abdominal sepsis work suggests that enhanced intraperitoneal (IP) clearance of Damage-Associated Molecular Patterns (DAMPs) improves outcome. Thus measuring the responses of DAMPs offers alternate potential insights and a representative DAMP, High Mobility Group Box-1 protein (HMGB-1), was considered. While IP biomediators are being recognized in critical illness/trauma, HMGB-1 behaviour has not been examined in open abdomen (OA) management. Methods. A modified protocol for HMGB-1 detection was used to examine plasma/IP fluid samples from 44 critically ill/injured OA patients enrolled in a randomized controlled trial comparing two negative pressure peritoneal therapies (NPPT): Active NPPT (ANPPT) and Barker's Vacuum Pack NPPT (BVP). Samples were collected and analyzed at the time of laparotomy and at 24 and 48 hours after. Results. There were no statistically significant differences in survivor versus nonsurvivor HMGB-1 plasma or IP concentrations at baseline, 24 hours, or 48 hours. However, plasma HMGB-1 levels tended to increase continuously in the BVP cohort. Conclusions. HMGB-1 appeared to behave differently between NPPT cohorts. Further studies are needed to elucidate the relationship of HMGB-1 and outcomes in septic/injured patients.

Highlights

  • Inflammatory biomediators enact diffuse end-organ damage in sepsis and the systemic inflammatory response syndrome (SIRS) but have been resistant to pharmacologic manipulation given their variable release, cross-reaction, and positive and negative feedback loops

  • The term Damage-Associated Molecular Patterns (DAMPs), a novel class of biomediators, describes molecules released by host cells upon lysis or injury, which signal for necrotic cell clearance by phagocytic cells of the immune system

  • There were no statistical differences between plasma and Peritoneal fluid (PF) High Mobility Group Box-1 protein (HMGB-1) concentrations at 24 and 48 hours after abdominal laparotomy (Table 1)

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Summary

Introduction

Inflammatory biomediators enact diffuse end-organ damage in sepsis and the systemic inflammatory response syndrome (SIRS) but have been resistant to pharmacologic manipulation given their variable release, cross-reaction, and positive and negative feedback loops. The term Damage-Associated Molecular Patterns (DAMPs), a novel class of biomediators, describes molecules released by host cells upon lysis or injury, which signal for necrotic cell clearance by phagocytic cells of the immune system. Circulating HMGB-1 released passively from necrotic cells can activate macrophage via Toll-like receptor 4 (TLR-4) to stimulate cytokine production [2, 5, 6]. Previous studies assessing various cytokines in the critically ill/injured have been uninformative in terms of translating to clinical care management. A modified protocol for HMGB-1 detection was used to examine plasma/IP fluid samples from 44 critically ill/injured OA patients enrolled in a randomized controlled trial comparing two negative pressure peritoneal therapies (NPPT): Active NPPT (ANPPT) and Barker’s Vacuum Pack NPPT (BVP). Further studies are needed to elucidate the relationship of HMGB-1 and outcomes in septic/injured patients

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