IntroductionBecause of ongoing controversy, renal and vital outcomes are compared between systemically administered unfractionated heparin and regional anticoagulation with citrate-buffered replacement solution in predilution mode, during continuous venovenous hemofiltration (CVVH) in critically ill patients with acute kidney injury (AKI).MethodsIn this multi-center randomized controlled trial, patients admitted to the intensive care unit requiring CVVH and meeting inclusion criteria, were randomly assigned to citrate or heparin. Primary endpoints were mortality and renal outcome in intention-to-treat analysis. Secondary endpoints were safety and efficacy. Safety was defined as absence of any adverse event necessitating discontinuation of the assigned anticoagulant. For efficacy, among other parameters, survival times of the first hemofilter were studied.ResultsOf the 139 patients enrolled, 66 were randomized to citrate and 73 to heparin. Mortality rates at 28 and 90 days did not differ between groups: 22/66 (33%) of citrate-treated patients died versus 25/72 (35%) of heparin-treated patients at 28 days, and 27/65 (42%) of citrate-treated patients died versus 29/69 (42%) of heparin-treated patients at 90 days (P = 1.00 for both). Renal outcome, i.e. independency of renal replacement therapy 28 days after initiation of CVVH in surviving patients, did not differ between groups: 29/43 (67%) in the citrate-treated patients versus 33/47 (70%) in heparin-treated patients (P = 0.82). Heparin was discontinued in 24/73 (33%) of patients whereas citrate was discontinued in 5/66 (8%) of patients (P < 0.001). Filter survival times were superior for citrate (median 46 versus 32 hours, P = 0.02), as were the number of filters used (P = 0.002) and the off time within 72 hours (P = 0.002). The costs during the first 72 hours of prescribed CVVH were lower in citrate-based CVVH.ConclusionsRenal outcome and patient mortality were similar for citrate and heparin anticoagulation during CVVH in the critically ill patient with AKI. However, citrate was superior in terms of safety, efficacy and costs.Trial registrationClinicaltrials.gov NCT00209378. Registered 13th September 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0472-6) contains supplementary material, which is available to authorized users.

IntroductionBlood transfusion is associated with increased morbidity and mortality in cardiac surgery patients, but cause-and-effect relations remain unknown. We hypothesized that blood transfusion is associated with changes in pulmonary and systemic inflammation and coagulation occurring in patients who do not meet the clinical diagnosis of transfusion-related acute lung injury (TRALI).MethodsWe performed a case control study in a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Cardiac surgery patients (n = 45) were grouped as follows: those who received no transfusion, those who received a restrictive transfusion (one two units of blood) or those who received multiple transfusions (at least five units of blood). Nondirected bronchoalveolar lavage fluid (BALF) and blood were obtained within 3 hours postoperatively. Normal distributed data were analyzed using analysis of variance and Dunnett's post hoc test. Nonparametric data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests.ResultsRestrictive transfusion increased BALF levels of interleukin (IL)-1β and D-dimer compared to nontransfused controls (P < 0.05 for all), and IL-1β levels were further enhanced by multiple transfusions (P < 0.01). BALF levels of IL-8, tumor necrosis factor α (TNFα) and thrombin-antithrombin complex (TATc) were increased after multiple transfusions (P < 0.01, P < 0.001 and P < 0.01, respectively) compared to nontransfused controls, but not after restrictive transfusions. Restrictive transfusions were associated with increased pulmonary levels of plasminogen activator inhibitor 1 compared to nontransfused controls with a further increase after multiple transfusions (P < 0.001). Concomitantly, levels of plasminogen activator activity (PAA%) were lower (P < 0.001), indicating impaired fibrinolysis. In the systemic compartment, transfusion was associated with a significant increase in levels of TNFα, TATc and PAA% (P < 0.05).ConclusionsTransfusion during cardiac surgery is associated with activation of inflammation and coagulation in the pulmonary compartment of patients who do not meet TRALI criteria, an effect that was partly dose-dependent, suggesting transfusion as a mediator of acute lung injury. These pulmonary changes were accompanied by systemic derangement of coagulation.

IntroductionThere are few data related to the effects of different sources of infection on outcome. We used the Sepsis Occurrence in Acutely ill Patients (SOAP) database to investigate differences in the impact of respiratory tract and abdominal sites of infection on organ failure and survival.MethodsThe SOAP study was a cohort, multicenter, observational study which included data from all adult patients admitted to one of 198 participating intensive care units (ICUs) from 24 European countries during the study period. In this substudy, patients were divided into two groups depending on whether, on admission, they had abdominal infection but no respiratory infection or respiratory infection but no abdominal infection. The two groups were compared with respect to patient and infection-related characteristics, organ failure patterns, and outcomes.ResultsOf the 3,147 patients in the SOAP database, 777 (25%) patients had sepsis on ICU admission; 162 (21%) had abdominal infection without concurrent respiratory infection and 380 (49%) had respiratory infection without concurrent abdominal infection. Age, sex, and severity scores were similar in the two groups. On admission, septic shock was more common in patients with abdominal infection (40.1% vs. 29.5%, P = 0.016) who were also more likely to have early coagulation failure (17.3% vs. 9.5%, P = 0.01) and acute renal failure (38.3% vs. 29.5%, P = 0.045). In contrast, patients with respiratory infection were more likely to have early neurological failure (30.5% vs. 9.9%, P < 0.001). The median length of ICU stay was the same in the two groups, but the median length of hospital stay was longer in patients with abdominal than in those with respiratory infection (27 vs. 20 days, P = 0.02). ICU (29%) and hospital (38%) mortality rates were identical in the two groups.ConclusionsThere are important differences in patient profiles related to the site of infection; however, mortality rates in these two groups of patients are identical.

BackgroundWe studied the value of routine biochemical variables albumin, C-reactive protein (CRP) and lactate dehydrogenase (LDH) to improve prediction and monitoring of acute respiratory distress syndrome (ARDS) severity in the intensive care unit.MethodsIn 101 critically ill patients, with or at risk for ARDS after new onset fever, data were collected on days (D) 0, 1, 2, and 7 after inclusion. ARDS was defined by the Berlin definition and lung injury score (LIS).ResultsAt baseline, 48 patients had mild to severe ARDS according to Berlin and 87 according to LIS (Rs = 0.54, P < 0.001). Low baseline albumin levels were moderately associated with maximum Berlin and LIS categories within 7 days; an elevated CRP level was moderately associated with maximum Berlin categories only. The day-by-day Berlin and LIS categories were inversely associated with albumin levels (P = 0.01, P < 0.001) and directly with CRP levels (P = 0.02, P = 0.04, respectively). Low albumin levels had monitoring value for ARDS severity on all study days (area under the receiver operating characteristic curve, AUROC, 0.62-0.82, P < 0.001-0.03), whereas supranormal CRP levels performed less . When the Berlin or LIS category increased, albumin levels decreased ≥1 g/L (AUROC 0.72-0.77, P = 0.001) and CRP increased ≥104 mg/L (only significant for Berlin, AUROC 0.69, P = 0.04). When the LIS decreased, albumin levels increased ≥1 g/L (AUROC 0.68, P = 0.02). LDH was higher in 28-day non-survivors than survivors (P = 0.007).ConclusionsOverall, albumin may be of greater value than CRP in predicting and monitoring the severity and course of ARDS in critically patients with or at risk for the syndrome after new onset fever. Albumin levels below 20 g/L as well as a decline over a week are associated with ARDS of increasing severity, irrespective of its definition. LDH levels predicted 28-day mortality.

BackgroundThere is ongoing controversy concerning optimum anticoagulation and buffering in continuous venovenous haemofiltration (CVVH). Regional anticoagulation with trisodium citrate also acting as a buffer in the replacement fluid has several advantages and disadvantages over prefilter citrate administration alone. We analysed a large cohort of patients with acute kidney injury (AKI) treated by the former method and hypothesized that it is safe and efficacious.MethodsPatients admitted at the intensive care unit with AKI and a high bleeding risk, without exclusion of liver disease, treated by CVVH with citrate in a custom-made replacement solution were prospectively included. Patient and CVVH characteristics, including citrate accumulation, were evaluated in outcome groups. A standardized mortality rate (SMR) was calculated using the simplified acute physiology score II.ResultsNinety-seven patients were included; metabolic control was adequate and did not differ between outcome groups, apart from lower pH/bicarbonate in non-survivors. Citrate accumulation was proven in 9% and was timely identified. These patients had about threefold higher plasma transaminases and higher CVVH dose and mortality. The hospital mortality was 60% with a SMR of 1.1 (95% confidence interval 0.90-1.40): age and hyperlactatemia, rather than CVVH-characteristics and citrate accumulation, predicted mortality in multivariable analysis.ConclusionIn critically ill, patients with AKI at high risk of bleeding, CVVH with citrate-containing replacement solution is safe and efficacious. The risk for citrate accumulation is 9% and best predicted by levels of transaminases. It carries, when citrate is discontinued, no attributable mortality.