Systemic impact on secondary brain aggravation due to ischemia/reperfusion injury in post-cardiac arrest syndrome: a prospective observational study using high-mobility group box 1 protein

Atsunori Sugita,Atsushi Sakurai,Kosaku Kinoshita,Satoshi Hori,Junko Yamaguchi,Tsukasa Kuwana,Nobutaka Chiba,Nami Sawada

doi:10.1186/s13054-017-1828-5

Atsunori Sugita, Atsushi Sakurai + Show 6 more

Open Access

https://doi.org/10.1186/s13054-017-1828-5

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Journal: Critical Care	Publication Date: Sep 26, 2017
Citations: 23	License type: open-access

Affiliation: Nihon University

Abstract

BackgroundIschemia/reperfusion injury (I/R) is an important pathophysiology of post-cardiac arrest syndrome (PCAS) against multiple organ dysfunction and mortality. The inflammatory response in PCAS causes systemic I/R. The purpose of this study was to demonstrate the pathophysiology of systemic I/R for secondary brain damage using the biomarkers high-mobility group box 1 (HMGB1), neuron-specific enolase (NSE), and interleukin-6 (IL-6).MethodsThis study was designed as a single-institution prospective observational study. Subjects were observed for 90 days, and neurological outcome was classified according to the Glasgow-Pittsburgh Cerebral Performance Categories Scale (CPC). Serum HMGB1, NSE, and IL-6 were evaluated for variability, correlation with each biomarker, or the Sequential Organ Function Assessment (SOFA) score and CPC at return of spontaneous circulation at 0, 24, 48, and 168 h.ResultsA total of 128 patients were enrolled in this study. Initial HMGB1 correlated with CPC (ρ = 0.27, p = 0.036) and SOFA score (ρ = 0.33, p < 0.001). The early phase of HMGB1 (0–24 h), all phases of IL-6, and the delayed phase of NSE (24–168 h) manifested poor neurological outcome. HMGB1 showed a significant correlation with NSE (ρ = 0.29, p = 0.002 at 0 h; ρ = 0.42, p < 0.001 at 24 h) and IL-6 (ρ = 0.36, p < 0.001 at 24 h).ConclusionsSerum HMGB1 for first 24 h after cardiac arrest was significantly correlated with SOFA score, NSE, and IL-6. This result suggests that systemic I/R may contribute to secondary brain aggravation. It is expected that research on HMGB1 focused on systemic I/R will help prevent aggravating neurological outcomes.

Highlights

Ischemia/reperfusion injury (I/R) is an important pathophysiology of post-cardiac arrest syndrome (PCAS) against multiple organ dysfunction and mortality
Inclusion criteria were (1) patients who achieved return of spontaneous circulation (ROSC) from out-of-hospital cardiac arrest (OHCA) and who were brought to the emergency and critical care department, regardless of cardiac or noncardiac etiology; and (2) patients who did not meet the exclusion criteria
Of 1361 patients with OHCA who were brought to the emergency room, 329 patients achieved ROSC

Summary

Introduction

Ischemia/reperfusion injury (I/R) is an important pathophysiology of post-cardiac arrest syndrome (PCAS) against multiple organ dysfunction and mortality. The inflammatory response in patients with post-cardiac arrest syndrome (PCAS) causes systemic ischemia/reperfusion injury (I/R), which may lead to multiple organ dysfunction and mortality, and is described as “sepsislike syndrome” [1]. It is related to increased permeability of the blood-brain barrier (BBB) [11] In this context, serum concentration of brain proteins such as the neuron-derived enzyme neuronspecific enolase (NSE), which is released after stroke [12] and cardiac arrest [13], has been assessed as a method of predicting secondary brain injury. NSE is an established and well-known measurement method used to predict poor neurological outcome in PCAS We speculate that these markers can identify possible cardiac arrest survivors and prognosis.

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