Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Glycocalyx and sepsis-induced alterations in vascular permeability

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

      Related collections

      Most cited references 76

      • Record: found
      • Abstract: found
      • Article: not found

      Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

      Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: found
        Is Open Access

        Sepsis biomarkers: a review

        Introduction Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. Methods We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. Results The search retrieved 3370 references covering 178 different biomarkers. Conclusions Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          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.
            Bookmark

            Author and article information

            Affiliations
            Department of Health Sciences, University of Florence, Section of Anesthesiology, Intensive Care and Pain Medicine, Viale Pieraccini, 6, 50139 Florence, Italy
            Contributors
            cosimochelazzi@gmail.com
            gianlucavilla1@gmail.com
            paola.mancinelli@hotmail.com
            araffaele.degaudio@unifi.it
            chiara.adembri@unifi.it
            Journal
            Crit Care
            Critical Care
            BioMed Central (London )
            1364-8535
            1466-609X
            28 January 2015
            28 January 2015
            2015
            : 19
            : 1
            4308932 741 10.1186/s13054-015-0741-z
            © Chelazzi et al.; licensee BioMed Central. 2015

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

            Categories
            Review
            Custom metadata
            © The Author(s) 2015

            Emergency medicine & Trauma

            Comments

            Comment on this article