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From Macrohemodynamic to the Microcirculation

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      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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      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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          Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock.

          To characterize the time course of microcirculatory alterations and their relation to outcome in patients with septic shock. Prospective, observational study. Thirty-one-bed, medico-surgical intensive care unit in a university hospital. Forty-nine patients with septic shock. The sublingual microcirculation was investigated with an orthogonal polarization spectral imaging device on the day of onset of septic shock (baseline) and each day until resolution of shock. Five sequences of 20 secs each were recorded and analyzed off-line by a semiquantitative method. Data were analyzed with nonparametric tests and presented as median (25th-75th percentiles). Three patients died after the resolution of shock from unrelated causes and were excluded. Of the other 46 patients, 26 survived and 20 died: 13 due to unresolving shock and seven due to persistent multiple organ failure after resolution of shock. At the onset of shock, survivors and nonsurvivors had similar vascular density (5.6 [4.7-7.0] vs. 6.2 [5.4-7.0]/mL; p = nonsignificant) and percentage of perfused small vessels (65.0 [53.1-68.9] vs. 58.4 [47.5-69.1]%; p = nonsignificant). Small vessel perfusion improved over time in survivors (analysis of variance, p <.05 between survivors and nonsurvivors) but not in nonsurvivors. Despite similar hemodynamic and oxygenation profiles and use of vasopressors at the end of shock, patients dying after the resolution of shock in multiple organ failure had a lower percentage of perfused small vessels than survivors (57.4 [46.6-64.9] vs. 79.3 [67.2-83.2]%; p =.02). Microcirculatory alterations improve rapidly in septic shock survivors but not in patients dying with multiple organ failure, regardless of whether shock has resolved.

            Author and article information

            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

            Crit Care Res Pract
            Crit Care Res Pract
            Critical Care Research and Practice
            Hindawi Publishing Corporation
            27 February 2013
            : 2013
            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.

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            Emergency medicine & Trauma


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