RESUMO
OBJECTIVE: Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen. We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis. DESIGN: This multicentre, randomised, controlled, single-blind trial was performed in two parallel groups. SETTING: Eight intensive care units in France. PARTICIPANTS: Adults with the phenotype of severe sepsis and no overt source of infection, negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission. INTERVENTION: The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians' clinical judgement without reference to procalcitonin values in the control arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of patients on antibiotics on day 5 postrandomisation. RESULTS: Over a 3-year period, 62/1250 screened patients were eligible for the study, of whom 31 were randomised to each arm; 4 later withdrew their consent. At day 5, 18/27 (67%) survivors were on antibiotics in the experimental arm, versus 21/26 (81%) controls (p=0.24; relative risk=0.83, 95% CI: 0.60 to 1.14). Only 8/58 patients (13%) had baseline procalcitonin <0.25 µg/l; in these patients, physician complied poorly with the algorithm. CONCLUSIONS: In intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen, the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure. However, the premature termination of the trial may not allow definitive conclusions.
RESUMO
PURPOSE: The aim of this experimental study is to investigate cardiovascular tolerance of blockade of beta-adrenergic receptors in an endotoxin model. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory in a university medical center. METHODS: Ten anesthetized, mechanically ventilated pigs were challenged with intravenous lipopolysaccharide (LPS) to achieve a status of profound hypodynamic shock. Systemic and pulmonary hemodynamics and cardiac output were continuously monitored throughout the 5-h study period, and blood samples were taken at baseline (T - 30 min), 1 h from the beginning of LPS infusion (T + 60 min), and every 2 h (T + 180 min and T + 300 min). Animals were randomly assigned to continuous intravenous esmolol infusion titrated to decrease heart rate by 20% or isotonic saline. RESULTS: Esmolol decreased heart rate by 20%, while in the saline group, heart rate increased by 7% and 22% at T + 180 min and T + 300 min, respectively (p < 0.001). In esmolol-treated animals, cardiac index decreased by 9% at T + 180 min and by 2% at T + 300 min, and in controls by 14% at T + 180 min and by 27% at T + 300 min (p = 0.870). In esmolol-treated animals, median (interquartile range, IQR) stroke index was 31 (6) and 47 (11) ml/min/m(2) at T + 180 min and T + 300 min, respectively, and decreased steadily from 45 (20) to 18 (13) ml/min/m(2) in controls (p = 0.030). There were no significant differences between groups for any other hemodynamics variables, except for systemic vascular resistance (SVR) (p = 0.017). CONCLUSIONS: In large animals with endotoxemic shock, continuous infusion of esmolol, a selective beta-1 adrenergic blocker, titrated to decrease heart rate by 20%, was well tolerated and may offset LPS-induced cardiac dysfunction by a preload positive effect.