Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study.

INTRODUCTION: Since data regarding new-onset atrial fibrillation (AF) in septic shock patients are scarce, the purpose of the present study was to evaluate the incidence and prognostic impact of new-onset AF in this patient group. METHODS: We prospectively studied all patients with new-onset AF and all patients suffering from septic shock in a non-cardiac surgical intensive care unit (ICU) during a 13 month period. RESULTS: During the study period, 687 patients were admitted to the ICU, of which 58 patients were excluded from further analysis due to pre-existing chronic or intermittent AF. In 49 out of the remaining 629 patients (7.8%) new-onset AF occurred and 50 out of the 629 patients suffered from septic shock. 23 out of the 50 patients with septic shock (46%) developed new-onset AF. There was a steady, significant increase in C-reactive protein (CRP) levels before onset of AF in septic shock patients. ICU mortality in septic shock patients with new-onset AF was 10/23 (44%) compared with 6/27 (22%) in septic shock patients with maintained sinus rhythm (SR) (P = 0.14). During a 2-year follow-up there was a trend towards an increased mortality in septic shock patients with new-onset AF, but the difference did not reach statistical significance (P = 0.075). The median length of ICU stay among surviving patients was longer in patients with new-onset AF compared to those with maintained SR (30 versus 17 days, P = 0.017). The success rate to restore SR was 86%. Failure to restore SR was associated with increased ICU mortality (71.4% versus 21.4%, P = 0.015). CONCLUSIONS: AF is a common complication in septic shock patients and is associated with an increased length of ICU stay among surviving patients. The increase in CRP levels before onset of AF may support the hypothesis that systemic inflammation is an important trigger for AF.

Effects of exogenous recombinant human granulocyte colony-stimulating factor (filgrastim, rhG-CSF) on neutrophils of critically ill patients with systemic inflammatory response syndrome depend on endogenous G-CSF plasma concentrations on admission.

OBJECTIVE: To investigate the effects of exogenous recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) application on the neutrophils of patients at risk of sepsis following major trauma or operation. DESIGN: Randomized controlled trial. SETTING: Surgical intensive care unit and research laboratory of a university hospital. PATIENTS: Twenty-seven patients with systemic inflammatory response syndrome (SIRS). INTERVENTIONS: Thirteen patients were treated with filgrastim (1 micro g.kg.24 h) for 10 days as a continuous infusion. Fourteen patients served as controls. MEASUREMENTS AND RESULTS: Surface expression of FcgammaR type I (CD64), phagocytosis of E. coli, and the E. coli-induced oxidative burst of neutrophils were tested by flow cytometry. On the first postoperative/posttraumatic day, endogenous G-CSF plasma concentrations were <300 pg/ml in seven controls (subgroup 1) and nine filgrastim patients (subgroup 3), and were already elevated with >500 pg/ml in seven controls (subgroup 2) and four filgrastim patients (subgroup 4). G-CSF values ( P=0.0026, subgroup 1/3; P=0.0167, 2/4), neutrophil counts ( P=0.0026, 1/3; P=0.0167, 2/4), and CD64 expression ( P=0.0013, 1/3) were higher in filgrastim-treated than non-treated subgroups, but not phagocytic and burst activities. From day zero to day 1, phagocytosis decreased in subgroups 1 (5/7 patients) and 3 (5/9), but increased in subgroups 2 (5/7) and 4 (3/4), and respiratory burst activity decreased in subgroup 3 (8/9). CONCLUSIONS: Besides activation of neutrophil maturation, low-dose rhG-CSF application in postoperative patients with SIRS has different effects on neutrophil functions, in part depending on already endogenously produced G-CSF.

Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit atheroma.

BACKGROUND: Lipid lowering may reduce acute coronary events in patients in part by reducing vascular inflammation. Oxidative stress induces endothelial cell (EC) expression of vascular cell adhesion molecule 1 (VCAM-1) and monocyte chemoattractant protein 1 (MCP-1) and reduces levels of atheroprotective NO, leading to monocyte recruitment and macrophage accumulation. This study tested the hypothesis that lipid lowering decreases oxidative stress and improves EC functions related to inflammatory cell accumulation. METHODS AND RESULTS: Rabbits consumed an atherogenic diet for 4 months to produce atheroma, followed by a purified chow diet for 16 months. Atherosclerotic aortas from hypercholesterolemic rabbits produced high levels of reactive oxygen species. Oxidized LDL (oxLDL) accumulated in atheroma underlying ECs that overexpress VCAM-1. In contrast, few if any ECs in atheroma stained for endothelial NO synthase (eNOS). Lipid lowering reduced reactive oxygen species production, oxLDL accumulation, and plasma levels of anti-oxLDL IgG. After lipid lowering, VCAM-1 and MCP-1 expression decreased, eNOS expression increased, and ECs exhibited a more normal ultrastructure. CONCLUSIONS: These results establish that lipid lowering can reduce oxidative stress and EC activation in vivo. These mechanisms may contribute to improvement in endothelial function and plaque stabilization observed clinically.