Viktor Foldi

Burn trauma induces early HMGB1 release in patients: Its correlation with cytokines

High-mobility group box protein 1 (HMGB1) is a nuclear protein that may be released actively from monocytes and macrophages or passively from necrotic or damaged cells. Several experimental data suggest that burn injury is accompanied by elevated plasma HMGB, but there are only few data available about its changes in burned patients. The aim of this study was to follow the time course and the prognostic value of plasma HMGB1 and cytokine changes in patients with severe burn injury affecting more than 10% of body surface area (n = 26). Blood samples were taken on admission and on the following 5 days. Plasma HMGB1 concentration was measured by the enzyme-linked immunosorbent assay method, whereas IL-6, IL-8, and IL-10 were assayed by the cytometric bead array kit. The HMGB1 and IL-10 concentrations were elevated on admission and gradually decreased thereafter. Significant differences were observed between survivors and nonsurvivors in HMGB1 (P < 0.01) and IL-10 (P < 0.001) concentrations on admission with higher levels in nonsurvivors. IL-6 and IL-8 started to increase markedly from day 2. Positive correlation (r = 0.669, P < 0.01) was found between burned body surface and HMGB1 on admission. Receiver operating characteristic analysis of data on admission showed that at a level of 16 ng/mL, HMGB1 indicated lethality, with 75.0% sensitivity and 85.7% specificity. Using the cutoff level of 14 pg/mL, IL-10 predicted intensive care unit mortality, with 85.7% sensitivity and 84.2% specificity. Very early HMGB1 and IL-10 release may have an important impact on the immune function of patients after burn trauma.

Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn

Oxidative stress and inflammation generate edema in burns. The aim of our study was to assess effect of N-acetylcysteine (NAC) on oxidative stress, inflammation, fluid requirement, multiple organ dysfunction (MOD) score and vasoactive drug requirement. In this study 15 patients were on standard therapy, whereas for other 15 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Levels of malondialdehyde, protein sulfhydril (PSH) groups, reduced gluthation (GSH), activity of myeloperoxidase, catalase and superoxide dismutase enzymes and induced free radical generating capacity were measured as well as concentrations of TNF-α, IL-6, IL-8, and IL-10. MOD score, use of vasopressor agents and fluid utilisation were recorded daily. NAC treatment increased GSH level on days 4-5 (p<0.05) and PSH level on days 2-6 (p<0.05) compared to controls. Plasma IL-6 was lower on days 4-5 (p<0.05), IL-8 on days 4-6 (p<0.05) and IL-10 on days 4-6 (p<0.05) in NAC group. NAC group received less catecholamines than controls (p<0.01) from day 4 without significant differences in MOD score. NAC treatment is associated with a diminished oxidative stress reflected in preserved antioxidant levels, lower inflammation mirrored in lower interleukin levels and less vasopressor requirement.

Time course of pro- and anti-inflammatory cytokine levels in patients with burns—Prognostic value of interleukin-10

INTRODUCTION Trends and the prognostic value of cytokine responses to severe burns have not been fully examined in humans. Therefore, the aim of this study was to determine the time course and prognostic value of pro- and anti-inflammatory cytokines in the immediate post-burn period. PATIENTS AND METHODS Blood samples were taken for measuring IL-1 beta, IL-6, IL-8, IL-10, IL-12p70 and TNF-alpha concentrations from patients with more than 20% burned surface area on admission and on 5 consecutive days. Development of sepsis was assessed using standard criteria twice a day. RESULTS IL-12p70 remained under assay detection levels in the study period. IL-1 beta and TNF-alpha could be detected in stimulated blood samples with higher levels in survivors (n=21). IL-6 on days 4-5 and IL-8 on days 4-6 in non-stimulated plasma showed significant elevation in non-survivors (n=18) whereas in stimulated blood its levels did not differ significantly. IL-10 levels were significantly higher in non-survivors during the study period in non-stimulated, and except day 6 in stimulated blood. Using the cut-off level of 14 pg ml(-1) for IL-10 predicted ICU mortality with 85.4% sensitivity and 84.2% specificity on admission. CONCLUSION Early anti-inflammatory excess had a bad prognosis for patients suffering from severe burns.

Effects of fluid resuscitation methods on burn trauma-induced oxidative stress.

The aim of the study was to analyze the oxidative stress response after severe burn injury. We studied the effect of two methods of fluid resuscitation regimes on the oxidative stress reaction. Sixteen patients were involved in the study. Inclusion criteria were the presence of flame burn injury affecting >20% of BSA and in-hospital fluid resuscitation started within 3 hours after injury. Patients were randomly assigned into two groups. In the first group (n = 8), the fluid resuscitation was guided by the hourly urine output and in the second (n = 8), by the intrathoracic blood volume index. Blood sample was taken from the patients at admission and on the following five mornings. White blood cell count normalized by the third day in both groups, but the relative number of granulocytes and lymphocytes significantly (P < .05) diverged between hourly urine output and intrathoracic blood volume index groups from the fourth day of trauma. Plasma malondialdehyde level (P < .05 vs control population), reactive oxygen species production in whole blood (P < .05 vs control population), and catalase activity were elevated, whereas glutathione, plasma sulfhydryl groups level (P < .05 vs control population), and superoxide dismutase enzyme activity lowered in both groups. Our results confirmed that burn injury induces pronounced oxidative stress. The main finding is that fluid resuscitation regimes have different impact on prooxidant status, mainly on the granulocyte function but not on the changes in endogenous antioxidants in burned patients.

Factors affecting fluid requirement on the first day after severe burn trauma.

Background:  Parkland formula (PF) is the most often used schema for calculating intravenous resuscitation fluid requirement in burn patients. Some studies have reported that PF underestimates the fluid requirement in 45–63% of patients. The aim of this retrospective study was to analyse factors influencing first‐day intravenous fluid replacement set for a targeted urinary output in severely burnt patients.

Extravascular lung water index as a sign of developing sepsis in burns.

Sepsis and multiple organ failure remain the leading cause of mortality and morbidity in burns. The aim of our study was to analyse the predictive value of extravascular lung water index (EVLWI) in the development of severe septic complications and mortality. The records of 28 patients with total burned surface area >20% were analysed (EVLWI, procalcitonin (PCT), intrathoracic blood volume index (ITBVI), positive end-expiratory pressure (PEEP), Baltimore Sepsis Scale (BaSS)). Diagnosis of infection (day 0) was based on consensus conference of the American Burn Association. EVLWI correlated with PCT (r=0.597), and PEEP (r=0.501) on day 0 and with BaSS (r=0.524) and MODS (r=0.513) from day 1. EVLWI was elevated (p<0.05) from one day before diagnosis of infection, PCT was higher (p<0.05) from day 0 only. ROC analysis for EVLWI on day -1 and for PCT on day 0 showed similar areas under curve (0.760; 0.766). EVLWI >9 ml kg(-1) on day -1 predicted sepsis (89% sensitivity, 72% specificity). After antibiotic treatment EVLWI remained high in non-survivors, decreased in survivors, whereas PCT decreased in both groups. Our data suggest that EVLWI is an early warning sign of developing infection and its continuous elevation can predict poor prognosis in burns.

Effect of N-acetylcysteine treatment on the expression of leukocyte surface markers after burn injury☆

Oxidative stress and inflammatory processes generate edema in burns. Treatment of consequent hypovolemia is a challenge. The aim of study was to assess if glutathione pro-drug N-acetylcysteine (NAC) can influence inflammation and fluid requirement. We also aimed to compare organ functions scores and vasoactive drug requirement. This prospective randomised study involved 28 patients with burn injury affecting more than 20% of body surface area. Fourteen patients were on standard therapy, whereas for other 14 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Leukocyte surface marker expressions were determined, multiple organ function scores, use of vasopressor agents and fluid requirements were recorded daily. Expression of CD11a (p < 0.05), CD18 (p < 0.05) and CD97 (p < 0.01) on the granulocytes were significantly lower in the NAC treated group, similarly to lymphocyte CD 49d (p < 0.05) and monocyte CD 49d (p < 0.01) and CD 97 (p < 0.05) expression. No significant difference was found in the fluid requirement between groups but patients the NAC group required less vasopressor and inotropic drugs from day 4. NAC treatment is associated with a less pronounced inflammation reflected in lower CD marker expression and vasopressor requirement.

Effects of fluid resuscitation methods on the pro- and anti-inflammatory cytokines and expression of adhesion molecules after burn injury.

Fluid resuscitation management can influence inflammatory response after burn injury. The aim of this study was to analyze the effects of two fluid resuscitation methods on the cytokine production and on the expression of the leukocyte surface markers. Thirty patients were included in this prospective randomized study with burn injury affecting more than 20% of the body surface area. Fluid resuscitation was guided by hourly urine output (HUO, n = 15) or by intrathoracic blood volume index (ITBVI, n = 15). Blood samples were taken on admission and on the next five consecutive mornings. Concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-α were measured in phorbol myristate acetate-stimulated and -nonstimulated samples. Leukocyte surface marker expressions (CD11a, CD11b, CD14, CD18, CD49d, and CD97) were also determined. In the ITBVI group, IL-6 levels on days 2 to 3 and IL-6/IL-10 ratios on days 2 to 3, and the IL-8/IL-10 ratios on days 3 to 5 were significantly higher than those in HUO group (P < .05). In the HUO group, IL-10 levels were significantly higher (P < .05) on days 4 and 5. Granulocyte CD11a levels on day 2, CD11b levels on days 4 to 6, lymphocyte CD11a on days 5 to 6, CD11b on days 3 to 6, CD49d on days 2 to 6, CD97 on day 6, monocyte CD11a, CD11b, CD18 levels on days 4 to 6, and CD14 levels on days 3 to 5 were significantly higher in the HUO group (P < .05). Our study suggests that ITBVI-guided fluid resuscitation of burned patients suppresses the shift toward anti-inflammatory imbalance and the expression of leukocyte surface markers more than HUO-guided resuscitation.

Time course of CD marker expression in patients with burns and its prognostic value.

INTRODUCTION Due to immune suppression sepsis has remained the leading cause of mortality after burns. CD marker expression in circulating blood has not been fully examined in humans. The aim of our study was to asses CD marker expression after burns and to compare it between survivors and non-survivors. PATIENTS AND METHODS Blood samples from all patients (n = 35) receiving intensive care treatment with more than 20% burned surface area were collected on admission and 5 consecutive days thereafter. Expressions of CD11a, CD11b, CD18, CD49d, CD97 and CD14 were measured on granulocytes, lymphocytes and monocytes. RESULTS Expressions of granulocytes CD11a (days 1-2), CD18 (day 1), lymphocytes CD11a (days 1-5), CD11b (days 2-4), CD18 (days 1-6), CD49d (days 1-6), CD97 (day 1), monocytes CD11a (days 1-6), CD11b (day 2 and 5-6), CD18 (days 1-6), CD49d (days 1-6), CD97 (days 1-2), and CD14 (days 4-6) were significantly lower in patients than in healthy controls. Expressions of granulocyte CD11a (days 3-6), lymphocytes CD11a (days 3-6), CD11b (days 4-6), CD18 (days 4-6), monocyte CD97 (days 3-6) were significantly higher in survivors (n = 20) than in non-survivors (n = 15). CONCLUSION These results suggest that burns is associated with immunosuppression and overwhelming anti-inflammatory processes may be signs of bad prognosis.