To determine the incidence and 28-d mortality rate for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) using the 1994 American-European Consensus Conference definitions, we prospectively screened every admission to all 21 adult intensive care units in the States of South Australia, Western Australia, and Tasmania (total population older than 15 yr of age estimated as 2,941,137), between October 1 and November 30, 1999. A total of 1,977 admissions were screened of which 168 developed ALI and 148 developed ARDS, which represents a first incidence of 34 and 28 cases per 100,000 per annum, respectively. The respective 28-d mortality rates were 32% and 34%. The most common predisposing factors for ALI were nonpulmonary sepsis (31%) and pneumonia (28%). Although the incidences of ALI and ARDS are higher and the mortality rates are lower than those reported from studies in other countries, multicenter international studies are required to exclude methodological differences as the cause for this finding.

Surfactant protein-B is a lung specific protein secreted into the air spaces by pulmonary epithelial type II cells that leaks into the bloodstream in increased amounts in patients with ARDS. To test whether elevated plasma levels of surfactant protein-B would predict the development of ARDS in patients with acute hypoxemic respiratory failure, plasma and lung injury scores were collected at study entry and daily thereafter for 3 d from 54 patients admitted to our intensive care unit. ARDS was defined as a new bilateral infiltrate on chest radiograph and a lung injury score > or = 2.5. Twenty patients developed ARDS, of whom seven died. Although the initial lung injury score was not predictive of ARDS, the initial plasma surfactant protein-B was predictive (area under the curve = 0.77 [0.63 to 0.90], nonparametric receiver-operating characteristic analysis). In this cohort, plasma surfactant protein-B was particularly predictive of ARDS when applied to patients suffering a direct lung insult (area under the curve = 0.87 [0.72 to 1.02]), with a sensitivity of 85% (95% CI: 55 to 98%) and specificity of 78% (40 to 97%) at a cutoff of 4,994 ng/ml.

Time dependence of predictors of survival in ALI/ARDS exists and must be appropriately modelled. The Cox model with time-varying covariates remains a flexible model in survival analysis of patients with acute severe illness.

BackgroundThe pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration is poorly understood. Urea plays an important role in the urinary concentrating mechanism and expression of the urea transporters UT-A1, UT-A2, UT-A3, UT-A4 and UT-B is essential for tubular urea reabsorption. The present study attempts to assess the regulation of renal urea transporters during severe inflammation in vivo. Materials and methods By agreement of the animal protection committee C57BL/6J, mice were injected with lipopolysaccharides (LPS, 10 mg/kg) or proinflammatory cytokines. Hemodynamic, renal parameters and the expression of renal urea transporters were investigated. To clarify the role of cytokines and renal ischemia in the regulation of renal urea transporters, experiments were performed with cytokine knockout mice, mice treated with low-dose LPS (1, 5 mg/kg) as a sepsis model without induction of hypotension, glucocorticoid-treated mice, and mice with renal artery clipping serving as a model for renal ischemia. Results and discussion LPS-injected mice (10 mg/kg) presented with reduced glomerular filtration rate, fractional urea excretion and inner medulla osmolality associated with a marked decrease in expression of UT-A1, UT-A2, UT-A3, UT-A4 and UT-B (Figure 1). Similar alterations were observed after application of TNFα, IL-1β, IFNγ or IL-6. LPS-induced downregulation of urea transporters was not affected in knockout mice with deficient TNFα, IL-receptor-1, IFNγ or IL-6. Glucocorticoid treatment inhibited LPS-induced increases of tissue TNFα, IL-1β, IFNγ or IL-6 concentration, diminished LPS-induced renal dysfunction and attenuated the downregulation of renal urea transporters. Injection of low-dose LPS (1, 5 mg/kg) also led to renal dysfunction paralleled by a downregulation of renal urea transporters without alterations in blood pressure. Renal ischemia induced by renal artery clipping did not influence the expression of urea transporters. Conclusion Our findings demonstrate downregulation of renal urea transporters that probably accounts for tubular dysfunction during sepsis. Furthermore, they suggest that downregulation of Figure 1 (abstract P1)Effect of lipopolysaccharide (LPS) (10 mg/kg), dexamethasone (10 mg/kg) and the combination of both on UT-A1, UT-A2, UT-A3, UT-A4 and UT-B mRNA in the kidney 6, 12 and 24 hours after intraperitoneal injection. Values are related to signals obtained for β-actin mRNA and presented as the percentage of vehicle control. Mean ± SEM of six animals per group. *P < 0.05 versus control, # P < 0.05 versus LPS treatment. S2Critical Care September 2007 Vol 11 Suppl 4 Sepsis 2007 renal urea transporters during LPS-induced acute renal failure is mediated by proinflammatory cytokines and is independent from renal ischemia due to sepsis-induced hypotension. Acknowledgement Supported by grants from the German Research Foundation (SFB 699). P2The role of regulatory T cells in the resistance of CCR4 knockout mice during severe sepsis Background Studies reveal that regul...