Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Clinical Trial
Protein C concentrate as adjuvant treatment in neonates with sepsis-induced coagulopathy: a pilot study.
The objective of the study is to describe safety and effects of protein C concentrate (PCConc) administration in neonates with sepsis-induced coagulopathy. Eighteen neonates (12 preterm and 6 full term) aged between 1 and 28 days who have severe sepsis (n = 6) or septic shock (n = 12), with coagulopathy and acquired protein C (PC) deficiency received PCConc (i.v. bolus of 100 IU/kg, followed by 50 IU/kg every 6 h for 72 h). Platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, C-reactive protein (CRP), antithrombin (AT), PC, CRP, and neonatal therapeutic intervention scoring system (NTISS) were assessed before and 24, 48, and 72 h after the study entry. ⋯ No adverse events were observed. This pilot study shows that in neonatal severe sepsis, normalization of PC levels is safe and probably effective in modulating the inflammatory response and in controlling coagulopathy. However, for the potential beneficial effects of PCConc administration on morbidity and mortality, a placebo-controlled, double-blind study is required.
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Acute respiratory distress syndrome (ARDS) is commonly diagnosed in intensive care units (ICUs), often in association with acute kidney injury. In this study, we compared the predictive value of outcome scoring systems: Acute Physiology and Chronic Health Evaluation IV (APACHE IV), earlier APACHE models, Sequential Organ Failure Assessment (SOFA), the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal failure (RIFLE) classification, and Acute Lung Injury score in critically ill patients with ARDS. We retrospectively abstracted data from the medical records of 135 critically ill ARDS patients in two medical ICUs of a tertiary care hospital from December 1999 to June 2006. ⋯ The area under the receiver operating characteristic curve for the APACHE IV score revealed good fit (Hosmer and Lemeshow goodness-of-fit test results) and discriminative power (area under the receiver operating characteristic curve, 0.792 ± 0.038; P < 0.001). The cumulative survival rates at 6-month follow-up after hospital discharge were significantly (P < 0.001) different among ARDS patients with APACHE IV mortality rate 35% or less and APACHE IV mortality rate higher than 35%. The APACHE IV score and RIFLEmax score are predictors of hospital mortality in ARDS patients, with APACHE IV demonstrating desirable properties of prognostic accuracy.
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A dramatic decrease in circulating lymphocyte number is regularly described after septic shock. However, it is unknown how early this alteration develops after diagnosis of shock and if it remains stable over time. Twenty-one septic shock patients with no comorbidities were included within 2 h after the beginning of vasopressive treatment. ⋯ At the time of diagnosis of shock and admission in the intensive care unit, septic patients already present with severe lymphopenia involving every lymphocyte subsets including CD4 T-cell subpopulations. No significant variation could be detected within the first 48 h. This should be taken into account in the forthcoming clinical trials testing immunomodulating therapies in septic shock patients.
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Diabetes mellitus is the leading comorbidity in patients with sepsis, but its impact upon survival and immunoinflammatory signaling in sepsis is undetermined. We investigated the effect of untreated diabetes mellitus upon survival and immunoinflammatory responses in the acute phase (days 1-5) of murine polymicrobial sepsis using the AKITA model of type 1 diabetes. Diabetic female C57BL/6-Ins2 (AKITA) and C57BL/6 wild-type (WT) mice underwent cecal ligation and puncture (CLP), blood (20 μL) was sampled for 5 days, and survival was monitored for 28 days. ⋯ A prelethal composite cytokine score was calculated on values obtained 24 h before death. This score was 3-fold lower for proinflammatory cytokines and 6-fold lower for anti-inflammatory mediators in the AKITA mice compared with the WT-Died mice but identical to the composite score in WT-Survived. These data demonstrate that untreated type I diabetes mellitus severely exacerbates sepsis mortality without inducing a prelethal release of systemic proinflammatory or anti-inflammatory cytokines.
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Interleukin 22 (IL-22) is a TH17-like cytokine known to specifically activate epithelial cells, thereby strengthening immune defense at host/environment interfaces. Animal studies suggest that IL-22 may play a crucial role in clinical sepsis. However, little is known about IL-22 in sepsis patients. ⋯ Here, we report, for the first time, a modest but significant elevation of serum IL-22 detectable in abdominal sepsis patients (P G 0.001). Median serum concentrations of IL-22 were 111.8 pg/mL, 3.4 or 2.0 pg/mL, and 9.3 pg/mL for abdominal sepsis patients, surgical control patients (presurgery or postsurgery), and healthy volunteers,respectively. Interleukin 22 produced in the course of abdominal sepsis may contribute to host defense and stabilization of mucosal barrier functions under conditions of systemic infection.