TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen.

BACKGROUND: Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis. METHODS: Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients. RESULTS: Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis. CONCLUSIONS: Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.

Monitoring of subcutaneous dalteparin in patients with renal insufficiency under intensive care: an observational study.

OBJECTIVE: The objective of this study was to investigate the pharmacodynamic parameters of dalteparin in patients with renal insufficiency under intensive care. MATERIALS AND METHODS: In this open, nonrandomized, nonblinded, prospective, single-dose observational study, 10 critically ill patients with renal insufficiency (mean creatinine clearance = 29.5 +/- 6.42 mL/min) were administered a single 5000-IU subcutaneous dose of dalteparin. RESULTS: Dalteparin blood levels were estimated indirectly over a 12-hour period by measuring anti-Xa activity and by performing a clotting assay known as the ATHU (AHEPA Thrombosis and Hemostasis Unit) test. Maximum anti-Xa activity (ie, 0.42 +/- 0.13 IU/mL) was achieved 4 hours after administration (in 8 of 10 patients). Adequate anticoagulant activity was maintained throughout the 12-hour dosage interval in all study patients. However, at time 0 hour of the study, 36 hours after the administration of a previous dose of dalteparin, considerable anti-Xa activity (ie, 0.39 +/- 0.11 IU/mL) was measured in 6 patients. A good correlation was found between anti-Xa activity and the results of the ATHU test. CONCLUSIONS: The presence of medium/severe edema and the concurrent administration of 1 to 3 inotropic drugs appear to contribute to a decrease in the rate of elimination of dalteparin, resulting in a greater-than-expected (as a result of decreased renal function) prolongation of its pharmacologic activity. We recommend that care be taken with repeated dosing of dalteparin in intensive care unit patients taking inotropic drugs until observed results can be confirmed.

Recombinant human erythropoietin therapy in critically ill patients: a dose-response study [ISRCTN48523317].

INTRODUCTION: The aim of this study was to assess the efficacy of two dosing schedules of recombinant human erythropoietin (rHuEPO) in increasing haematocrit (Hct) and haemoglobin (Hb) and reducing exposure to allogeneic red blood cell (RBC) transfusion in critically ill patients. METHOD: This was a prospective, randomized, multicentre trial. A total of 13 intensive care units participated, and a total of 148 patients who met eligibility criteria were enrolled. Patients were randomly assigned to receive intravenous iron saccharate alone (control group), intravenous iron saccharate and subcutaneous rHuEPO 40,000 units once per week (group A), or intravenous iron saccharate and subcutaneous rHuEPO 40,000 units three times per week (group B). rHuEPO was given for a minimum of 2 weeks or until discharge from the intensive care unit or death. The maximum duration of therapy was 3 weeks. RESULTS: The cumulative number of RBC units transfused, the average numbers of RBC units transfused per patient and per transfused patient, the average volume of RBCs transfused per day, and the percentage of transfused patients were significantly higher in the control group than in groups A and B. No significant difference was observed between group A and B. The mean increases in Hct and Hb from baseline to final measurement were significantly greater in group B than in the control group. The mean increase in Hct was significantly greater in group B than in group A. The mean increase in Hct in group A was significantly greater than that in control individuals, whereas the mean increase in Hb did not differ significantly between the control group and group A. CONCLUSION: Administration of rHuEPO to critically ill patients significantly reduced the need for RBC transfusion. The magnitude of the reduction did not differ between the two dosing schedules, although there was a dose response for Hct and Hb to rHuEPO in these patients.