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      From Macrohemodynamic to the Microcirculation

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          Abstract

          ICU patients need a prompt normalization of macrohemodynamic parameters. Unfortunately, this optimization sometimes does not protect patients from organ failure development. Prevention or treatment of organ failure needs another target to be pursued: the microcirculatory restoration. Microcirculation is the ensemble of vessels of maximum 100  μm in diameter. Nowadays the Sidestream Dark Field (SDF) imaging technique allows its bedside investigation and a recent round-table conference established the criteria for its evaluation. First, microcirculatory derangements have been studied in sepsis: they are mainly characterized by a reduction of vessel density, an alteration of flow, and a heterogeneous distribution of perfusion. Endothelial malfunction and glycocalyx rupture were proved to be the main reasons for the observed microthrombi, capillary leakage, leukocyte rolling, and rouleaux phenomenon, even if further studies are necessary for a better explanation. Therapeutic approaches targeting microcirculation are under investigation. Microcirculatory alterations have been recently demonstrated in other diseases such as hypovolemia and cardiac failure but this issue still needs to be explored. The aim of this paper is to gather the already known information, focus the reader's attention on the importance of microvascular physiopathology in critical illness, and prompt him to actively participate to achieve a more comprehensive understanding of the issue.

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          Most cited references 70

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          Early goal-directed therapy in the treatment of severe sepsis and septic shock.

          Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001). Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.
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            Microvascular blood flow is altered in patients with sepsis.

            Microvascular blood flow alterations are frequent in animal models of sepsis and may impair tissue oxygenation. We hypothesized that alterations of the microcirculation are present in patients with sepsis. We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 10 healthy volunteers, 16 patients before cardiac surgery, 10 acutely ill patients without sepsis (intensive care unit control subjects), and 50 patients with severe sepsis. The effects of topical application of acetylcholine (10(-2) M) were tested in 11 patients with sepsis. In each subject, five to seven sublingual areas were recorded and analyzed semiquantitatively. Data were analyzed with nonparametric tests and are presented as medians (25th-75th percentiles). No significant difference in microvascular blood flow was observed between healthy volunteers and patients before cardiac surgery or intensive care unit control subjects. The density of all vessels was significantly reduced in patients with severe sepsis (4.5 [4.2-5.2] versus 5.4 [5.4-6.3]/mm in volunteers, p < 0.01). The proportion of perfused small (< 20 microm) vessels was reduced in patients with sepsis (48 [33-61] versus 90 [89-92]% in volunteers, p < 0.001). These alterations were more severe in nonsurvivors. The topical application of acetylcholine totally reversed these alterations. In conclusion, microvascular blood flow alterations are frequent in patients with sepsis and are more severe in patients with a worse outcome.
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              Drotrecogin alfa (activated) in adults with septic shock.

              There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81). DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).
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                Author and article information

                Affiliations
                1Sezione di Anestesia e Rianimazione, Dipartimento di Scienze Biomediche e Sanità Pubblica, Università Politecnica delle Marche, Ancona, Via Tronto 10, 60020 Torrette (Ancona), Italy
                2AOU Ospedali Riuniti, Via Conca 71, 60020 Ancona, Italy
                3Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
                Author notes

                Academic Editor: M. P. Fink

                Journal
                Crit Care Res Pract
                Crit Care Res Pract
                CCRP
                Critical Care Research and Practice
                Hindawi Publishing Corporation
                2090-1305
                2090-1313
                2013
                27 February 2013
                : 2013
                23509621 3600213 10.1155/2013/892710
                Copyright © 2013 Abele Donati et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review Article

                Emergency medicine & Trauma

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