Search

Aim of the Study: To study plasma concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and S-100B during intensive care after out-of-hospital cardiac arrest from ventricular fibrillation (OHCA-VF), and their associations with the duration of ischemia, organ dysfunction and long-term neurological outcome., Materials and Methods: A 12-month prospective observational multicentre study was conducted in 21 Finnish intensive care units in 2011. IL-6, hs-CRP and S-100B were measured at 0-6 h, 24 h, 48 h and 96 h after ICU admission. Associations with the time to return of spontaneous circulation (ROSC), sequential organ failure assessment (SOFA) scores divided into tertiles and 12-month cerebral performance category (CPC) were tested., Results: Of 186 OHCA-VF patients included in the study, 110 (59.1%) patients survived with good neurological outcome (CPC 1-2) 12 months after cardiac arrest. Admission plasma concentrations of IL-6 but not hs-CRP were higher with prolonged time to ROSC (p<0.001, 0.203, respectively), in patients with subsequent higher SOFA scores (p<0.001, 0.069) and poor long-term neurological outcome (CPC 3-5) (p<0.001, 0.315). S-100B concentrations over time were higher in patients with CPC of 3-5 (p<0.001). The area under the curve for prediction of poor 12-month outcome for admission levels was 0.711 IL-6, 0.663 for S-100B and 0.534 for hs-CRP. With multivariate logistic regression analysis only admission IL-6 (p=0.046, OR 1.006, 95% CI 1.000-1.011/ng/L) was an independent predictor of poor neurological outcome., Conclusion: Admission high IL-6, but not hs-CRP or S-100B, is associated with extra-cerebral organ dysfunction and along with age and time to ROSC are independent predictors for 12-month poor neurologic outcome (CPC 3-5)., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Being a central link between inflammation and coagulation, tissue factor (TF) and its inhibitor (TFPI) might be associated with the severity of acute pancreatitis (AP) and the development of organ failure (OF)., Methods: The study comprises 9 severe AP patients with OF and 24 reference patients (11 mild AP and 13 severe AP without OF). Plasma samples were collected on admission. TF-induced thrombin generation in plasma samples was studied using the thrombogram method. In vivo thrombin generation was estimated by prothrombin fragment F1+2. Free and total TFPI levels were measured. To evaluate coagulation status the activated partial thromboplastin time, prothrombin time, platelet count, D-dimer, fibrinogen, antithrombin (AT) 3 and protein C (PC) were determined., Results: There was no significant difference in F1+2 levels between the patient groups. Patients with severe AP tended to show low platelet counts, PC and AT3 levels, and high D-dimer levels. In 11 patients the standard TF stimulation did not trigger thrombin generation in the thrombogram. All deaths occurred in these patients. Free TFPI levels and free/total TFPI ratios were significantly higher in these patients and in non-survivors., Conclusion: Failure of TF-initiated thrombin generation in the thrombogram assay explained by high levels of circulating free TFPI may be associated with OF and mortality in AP. and IAP., (Copyright © 2011 S. Karger AG, Basel.)

Introduction: Sepsis-related multiple organ dysfunction is a common cause of death in the intensive care unit. The effect of sepsis on markers of tissue repair is only partly understood. The aim of this study was to measure markers of collagen synthesis and degradation during sepsis and investigate the association with disease severity and outcome., Methods: Forty-four patients with severe sepsis participated in the study and 15 volunteers acted as controls. Blood samples were collected for 10 days after the first sepsis-induced organ dysfunction and after three and six months. Procollagen type I and III aminoterminal propeptides (PINP and PIIINP) and cross-linked telopeptides of type I collagen (ICTP) were measured., Results: The PIIINP concentration was elevated in the septic patients (8.8 microg/L, 25th to 75th percentile = 6.8 to 26.0) when compared with controls (3.0 microg/L, 25th to 75th percentile = 2.7 to 3.3; P < 0.001) on day one. Maximum serum PIIINP concentrations during sepsis were higher in non-survivors compared with survivors (26.1 microg/L, 25th to 75th percentile = 18.7 to 84.3; vs. 15.1 microg/L, 25th to 75th percentile = 9.6 to 25.5; P = 0.033) and in multiple organ failure (MOF) compared with multiple organ dysfunction syndrome (MODS) (24.2 ug/L, 25th to 75th percentile = 13.4 to 48.2; vs. 8.9 microg/L, 25th to 75th percentile = 7.4 to 19.4; P = 0.002). Although the PINP values of the septic patients remained within the laboratory reference values, patients with MOF had higher values than patients with MODS (79.8, 25th to 75th percentile = 44.1 to 150.0; vs.40.4, 25th to 75th percentile = 23.6 to 99.3; P = 0.007). Day one ICTP levels were elevated in septic patients compared with the controls (19.4 microg/L, 25th to 75th percentile = 12.0 to 29.8; vs. 4.1 microg/L, 25th to 75th percentile = 3.4 to 5.0; P < 0.001)., Conclusions: Markers of collagen metabolism are increased in patients with severe sepsis and can be investigated further as markers of disease severity and outcome.

Background: Vascular endothelial growth factor (VEGF) levels have been shown to be elevated in severe sepsis. We investigated the value of VEGF in predicting organ dysfunction and hospital mortality in adult patients with severe sepsis., Methods: We conducted a prospective observational cohort study in 24 closed multidisciplinary intensive care units (ICU) in Finland. All ICU admission episodes (4500) were screened for severe sepsis from November 1, 2004, to February 28, 2005. Patients were eligible if they fulfilled the criteria for severe sepsis., Results: Severe sepsis was found in 470 patients. Laboratory samples were obtained after informed consent from 250 patients at study entry (day 0) and from 215 patients after 72 h. These samples were compared with samples from 30 healthy individuals. The ICU mortality was 13.2% and hospital mortality 26%. Median serum VEGF concentrations on day 0 were 423 pg/mL (interquartile range [IQR] 159 and 858 pg/mL), and after 72 h were 521 pg/mL (IQR 182 and 1092 pg/mL), which were both higher than in healthy controls (P = 0.029 and 0.003, respectively). Low VEGF concentrations were associated with more severe renal and hematological dysfunction (Sequential Organ Failure Assessment scores 3-4 compared with scores 0-2). VEGF concentrations in day 0 and after 72 h were lower in nonsurvivors (P = 0.01 and <0.01, respectively) than in survivors, but the receiver operating characteristic curve analyses of concentrations of VEGF on day 0 and at 72 h revealed areas under the curve of 0.58 and 0.63 (95% confidence limits 0.48-0.68 and 0.54-0.72, P = 0.1 and 0.009, respectively)., Conclusions: VEGF concentrations are increased in patients with severe sepsis. Low concentrations are associated with hematological and renal dysfunction. VEGF concentrations were lower in nonsurvivors than in survivors, but did not adequately predict hospital mortality in patients with severe sepsis.

Objective: To study the predictive value of high mobility group box-1 protein (HMGB1) and hospital mortality in adult patients with severe sepsis., Study Design: Prospective observational cohort study in 24 ICUs in Finland., Patients: Two hundred and forty-seven adult patients with severe sepsis., Measurements and Main Results: Blood samples for HMGB1 analyses were drawn from 247 patients at baseline and from 210 patients 72 h later. The mean APACHE II and SAPS II scores were 24 (SD 9) and 44 (SD 17), respectively. The hospital mortality was 26%. The serum HMGB1 concentrations were measured first by semi-quantitative Western immunoblotting (WB) analysis. The median HMGB1 concentration on day 0 was 108% (IQR 98.5-119) and after 72 h 107% (IQR 98.8-120), which differed from healthy controls (97.5%, IQR 91.3-106.5; p=0.028 and 0.019, respectively). The samples were re-analysed by ELISA (in a subgroup of 170 patients) to confirm the results by WB. The median concentration in healthy controls was 0.65 ng/ml (IQR 0.51-1.0). This was lower than in patients with severe sepsis (3.6 ng/ml, IQR 1.9-6.5, p< 0.001). HMGB1 concentrations (WB and ELISA) did not differ between hospital survivors and non-survivors. In ROC analyses for HMGB1 levels (WB) on day 0 and 72 h with respect to hospital mortality, the areas under the curve were 0.51 and 0.56 (95% CI 0.40-0.61 and 0.47-0.65)., Conclusions: Serum HMGB1 concentrations were elevated in patients with severe sepsis, but did not differ between survivors and non-survivors and did not predict hospital mortality.

Objective: To investigate the concentration of cell-free plasma DNA and its association with organ dysfunction and hospital mortality in intensive care unit patients., Design and Setting: Prospective cohort study in a medical and two medical-surgical intensive care units in a university hospital., Patients: 228 critically ill patients admitted to the ICUs between January 2004 and July 2005., Measurements and Results: Blood samples were collected as soon as possible after ICU admission, the following morning, and 48[Symbol: see text]h after the second sample. The cell-free plasma DNA was measured by real-time quantitative PCR assay for the beta-globin gene. Physiological and mortality data were collected to the clinical database. Hospital mortality rate and SOFA scores were primary outcome measures. The maximum plasma DNA concentrations were correlated significantly with APACHE II points and with maximum SOFA scores. Cell-free plasma DNA concentrations were higher in hospital non-survivors than in survivors (median 9,366 vs. 6,506 GE/ml). Using logistic regression analysis, the maximum plasma DNA was an independent predictor of hospital mortality., Conclusions: The maximum plasma DNA concentration measured during the first 96[Symbol: see text]h of intensive care is associated with the degree of organ dysfunction and disease severity. Moreover, the maximum DNA concentration is independently associated with hospital mortality.