Early goal-directed resuscitation of patients with septic shock: current evidence and future directions

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials

Dielectric study of the glass transition: correlation with calorimetric data

The glass transition in amorphous poly(ethylene terephthalate) is studied by thermally stimulated depolarization currents (TSDC) and differential scanning calorimetry (DSC). The ability of TSDC to decompose a distributed relaxation, as the glass transition, into its elementary components is demonstrated. Two polarization techniques, windows polarization (WP) and non-isothermal windows polarization (NIW), are employed to assess the influence of thermal history in the results. The Tool-Narayanaswami-Moynihan (TNM) model has been used to fit the TSDC spectra. The most important contributions to the relaxation comes from modes with non-linearity (x) around 0.7. Activation energies yield by this model are located around 1eV for polarization temperature (Tp) below 50C and they raise up to values higher than 8eV as Tp increases (up to 80C). There are few differences between results obtained with WP and NIW but, nonetheless, these are discussed. The obtained kinetic parameters are tested against DSC results in several conditions. Calculated DSC curves at several cooling and heating rates can reproduce qualitatively experimental DSC results. These results also demonstrate that modelization of the non-equilibrium kinetics involved in TSDC spectroscopy is a useful experimental tool for glass transition studies in polar polymers.Comment: 13 pages, 2 tables, 10 figures; minor change

The Longitudinal Stability of Intense Non-Relativistic Particle Bunches in Resistive Structures

The longitudinal stability of intense particle bunches is investigated theoretically in the limit of small wall resistivity compared to total reactance. It is shown that both in the absence of resistivity and to lowest order in the resistance that an intense bunch is stable against longitudinal collective modes. An expression is derived for the lowest order instability rate. Application of these results are made to drivers for heavy ion inertial fusion

Muon Colliders

Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should thus be regarded as complementary. Parameters are given of 4 TeV and 0.5 TeV high luminosity \mumu colliders, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders, starting from the proton accelerator needed to generate the muons and proceeding through muon cooling, acceleration and storage in a collider ring. Problems of detector background are also discussed.Comment: 28 pages, with 12 postscript figures. To be published Proceedings of the 9th Advanced ICFA Beam Dynamics Workshop, AIP Pres

Nitrous oxide does not produce a clinically important sparing effect during closed-loop delivered propofol-remifentanil anaesthesia guided by the bispectral index: a randomized multicentre study†‡

Background Nitrous oxide (N2O) offers both hypnotic and analgesic characteristics. We therefore tested the hypothesis that N2O administration decreases the amount of propofol and remifentanil given by a closed-loop automated controller to maintain a similar bispectral index (BIS). Methods In a randomized multicentre double-blind study, patients undergoing elective surgery were randomly assigned to breathe 60% inspired N2O (N2O group) or 40% oxygen (AIR group). Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40-60 (BIS40-60). The primary outcomes were propofol and remifentanil consumption, with reductions of 20% in either being considered clinically important. Results A total of 302 patients were randomized to the N2O group and 299 to the AIR group. At similar BIS40-60 [79 (67-86)% vs 76 (65-85)%], N2O slightly decreased propofol consumption [4.5 (3.7-5.5) vs 4.8 (4.0-5.9) mg kg−1 h−1, P=0.032], but not remifentanil consumption [0.17 (0.12-0.23) vs 0.18 (0.14-0.24) µg kg−1 min−1]. For the subgroups of men, at similar BIS40-60 [80 (72-88)% vs 80 (70-87)%], propofol [4.2 (3.4-5.3) vs 4.4 (3.6-5.4) mg kg−1 h−1] and remifentanil [0.19 (0.13-0.25) vs 0.18 (0.15-0.23) µg kg−1 min−1] consumptions were similar in the N2O vs AIR group, respectively. For the subgroups of women, at similar BIS40-60 [76 (64-84)% vs 72 (62-82)%], propofol [4.7 (4.0-5.8) vs 5.3 (4.5-6.6) mg kg−1 h−1, P=0.004] and remifentanil [0.18 (0.13-0.25) vs 0.20 (0.15-0.27) µg kg−1 min−1, P=0.029] consumptions decreased with the co-administration of N2O. Conclusions With automated drug administration titrated to comparable BIS, N2O only slightly reduced propofol consumption and did not reduce remifentanil consumption. There was a minor gender dependence, but not by a clinically important amount. Clinical trial registration This study was registered at ClinicalTrials.gov, number NCT0054720

On the re-acceleration of bunched beams

We examine the re-acceleration of a bunched beam through a linear induction accelerator (LIA) cavity, with attention to the energy lost through coupling to the TM modes of the structure. We find that the energy lost at 1 kA peak current is a small fraction of the boost which the LIA is designed to impart. We discuss implications for a Relativistic Klystron or Free Electron Laser (FEL) version of the Two-Beam Accelerator (TBA). 18 refs., 5 figs., 1 tab