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

• Published in: Critical Care Vol. 21; no. 1; pp. 247 - 12
• Main Authors: Sugita, Atsunori, Kinoshita, Kosaku, Sakurai, Atsushi, Chiba, Nobutaka, Yamaguchi, Junko, Kuwana, Tsukasa, Sawada, Nami, Hori, Satoshi
• Format: Journal Article
• Language: English
• Published: England Springer Science and Business Media LLC 26.09.2017; BioMed Central Ltd; BioMed Central; BMC
• Subjects: Aged; Aged, 80 and over; Biomarkers; Biomarkers - analysis; Biomarkers - blood; Blood pressure; Brain damage; Cardiac arrest; Cardiopulmonary resuscitation; Councils; CPR; Critical care; Emergency medical care; Enzymes; Female; Health aspects; Heart Arrest; Heart Arrest - complications; Heart Arrest - drug therapy; Heart attacks; HMGB1; HMGB1 Protein; HMGB1 Protein - analysis; HMGB1 Protein - blood; Humans; IL-6; Interleukin-6; Interleukin-6 - analysis; Interleukin-6 - blood; Ischemia; Kaplan-Meier Estimate; Male; Medical emergencies. Critical care. Intensive care. First aid; Medical prognosis; Middle Aged; Mortality; NSE; Observational studies; Observations; Organ Dysfunction Scores; Patient outcomes; Phosphopyruvate Hydratase; Phosphopyruvate Hydratase - analysis; Phosphopyruvate Hydratase - blood; Physiological aspects; Post-cardiac arrest syndrome; Prospective Studies; Proteins; RC86-88.9; Reperfusion Injury; Reperfusion Injury - drug therapy; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; Rodents; SOFA score; Statistics, Nonparametric; Stroke; Systemic ischemia/reperfusion injury; NSE; Systemic ischemia/reperfusion injury; Post-cardiac arrest syndrome; SOFA score; Secondary brain injury; HMGB1; IL-6
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1466-609X; 1366-609X
• DOI: 10.1186/s13054-017-1828-5

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 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). This 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. A 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). Serum 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.