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Journal ArticleDOI

Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome.

TL;DR: Microcirculatory alterations are stronger predictors of outcome than global hemodynamic variables in patients with severe sepsis.
Abstract: Objectives: Sepsis induces microvascular alterations that may play an important role in the development of organ dysfunction. However, the relationship of these alterations to systemic variables and outcome is still not well defined. We investigated which factors may influence microcirculatory alterations in patients with severe sepsis and whether these are independently associated with mortality. Design: Analysis of prospectively collected data from previously published studies by our group. Setting: A 36-bed, medicosurgical university hospital Department of Intensive Care. Patients: A total of 252 patients with severe sepsis in whom the sublingual microcirculation was visualized using orthogonal polarization spectral or sidestream darkfield imaging techniques. Measurements and Main Results: Microcirculatory measurements were obtained either early, within 24 h of the onset of severe sepsis (n = 204), or later, after 48 h (n = 48). When multiple measurements were obtained, only the first was considered. Although global hemodynamic variables were relatively preserved (mean arterial pressure 70 [65–77] mm Hg, cardiac index 3.3 [2.7–4.0] L/min.m 2 , and Svo 2 68.3 [62.8–74.7]%),
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Journal ArticleDOI
TL;DR: In the setting of established acute kidney injury, fluid management can be challenging, and impaired capacity of urine output and urine concentration and dilution should be taken into consideration when designing fluid therapy.
Abstract: Over 50% of the human body is comprised of fluids that are distributed in defined compartments. Although compartmentalized, these fluids are dynamically connected. Fluids, electrolytes, and acid-base

1,000 citations

Journal ArticleDOI
01 Mar 2016-Shock
TL;DR: The response of the endothelial cell lining to sepsis in the kidney, liver, and lung is discussed and evidence as to whether the EC response toSepsis is adaptive or maladaptive is discussed.
Abstract: Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014.

425 citations


Cites background from "Microcirculatory alterations in pat..."

  • ...Several recent studies in septic patients have shown that microcirculatory alterations are closely associated with organ failure and mortality (49, 50),...

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  • ...In addition, several trials have demonstrated an association between the severity of microvascular dysfunction and the development of organ dysfunction (46, 87, 88) and mortality (49, 83, 89)....

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Journal ArticleDOI
TL;DR: Current treatment for sepsis aims to limit the development of organ dysfunction by providing rapid control of infection, haemodynamic stabilization and organ support when possible to ensure recovery of organ function.
Abstract: Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Knowledge of the pathophysiology of organ failure in sepsis is crucial for optimizing the management and treatment of patients and for the development of potential new therapies. In clinical practice, six major organ systems - the cardiovascular (including the microcirculation), respiratory, renal, neurological, haematological and hepatic systems - can be assessed and monitored, whereas others, such as the gut, are less accessible. Over the past 2 decades, considerable amounts of new data have helped improve our understanding of sepsis pathophysiology, including the regulation of inflammatory pathways and the role played by immune suppression during sepsis. The effects of impaired cellular function, including mitochondrial dysfunction and altered cell death mechanisms, on the development of organ dysfunction are also being unravelled. Insights have been gained into interactions between key organs (such as the kidneys and the gut) and organ-organ crosstalk during sepsis. The important role of the microcirculation in sepsis is increasingly apparent, and new techniques have been developed that make it possible to visualize the microcirculation at the bedside, although these techniques are only research tools at present.

328 citations

Journal ArticleDOI
TL;DR: A personal viewpoint of the shortcoming of conventional hemodynamic resuscitation procedures in achieving organ perfusion and tissue oxygenation following conditions of shock and cardiovascular compromise is presented, and how to optimize the volume of fluid to maximize the oxygen-carrying capacity of the microcirculation to transport oxygen to the tissues is proposed.
Abstract: This article presents a personal viewpoint of the shortcoming of conventional hemodynamic resuscitation procedures in achieving organ perfusion and tissue oxygenation following conditions of shock and cardiovascular compromise, and why it is important to monitor the microcirculation in such conditions. The article emphasizes that if resuscitation procedures are based on the correction of systemic variables, there must be coherence between the macrocirculation and microcirculation if systemic hemodynamic-driven resuscitation procedures are to be effective in correcting organ perfusion and oxygenation. However, in conditions of inflammation and infection, which often accompany states of shock, vascular regulation and compensatory mechanisms needed to sustain hemodynamic coherence are lost, and the regional circulation and microcirculation remain in shock. We identify four types of microcirculatory alterations underlying the loss of hemodynamic coherence: type 1, heterogeneous microcirculatory flow; type 2, reduced capillary density induced by hemodilution and anemia; type 3, microcirculatory flow reduction caused by vasoconstriction or tamponade; and type 4, tissue edema. These microcirculatory alterations can be observed at the bedside using direct visualization of the sublingual microcirculation with hand-held vital microscopes. Each of these alterations results in oxygen delivery limitation to the tissue cells despite the presence of normalized systemic hemodynamic variables. Based on these concepts, we propose how to optimize the volume of fluid to maximize the oxygen-carrying capacity of the microcirculation to transport oxygen to the tissues.

327 citations


Cites background or result from "Microcirculatory alterations in pat..."

  • ...Many studies in the literature have described conditions of a loss of hemodynamic coherence where resuscitation resulted in a normalization of systemic hemodynamic variables but did not lead to a parallel improvement in microcirculatory perfusion and oxygenation [10-14]....

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  • ...[10,32] showed in several studies in septic patients that patients with such a type 1 loss of hemodynamic coherence between microcirculatory alterations and systemic hemodynamic variables were associated with adverse outcomes....

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  • ...Clinical studies monitoring sublingual microcirculation using hand-held videomicroscopy have identified the lack of hemodynamic coherence in several studies, a condition associated with increased morbidity and mortality [10-13]....

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Journal ArticleDOI
TL;DR: This review discusses the various mechanisms that are potentially involved in their development and the implications of these alterations in sepsis, and investigates therapies to specifically target the microcirculation.
Abstract: Multiple experimental and human trials have shown that microcirculatory alterations are frequent in sepsis. In this review, we discuss the various mechanisms that are potentially involved in their development and the implications of these alterations. Endothelial dysfunction, impaired inter-cell communication, altered glycocalyx, adhesion and rolling of white blood cells and platelets, and altered red blood cell deformability are the main mechanisms involved in the development of these alterations. Microcirculatory alterations increase the diffusion distance for oxygen and, due to the heterogeneity of microcirculatory perfusion in sepsis, may promote development of areas of tissue hypoxia in close vicinity to well-oxygenated zones. The severity of microvascular alterations is associated with organ dysfunction and mortality. At this stage, therapies to specifically target the microcirculation are still being investigated.

292 citations


Cites background from "Microcirculatory alterations in pat..."

  • ...In a large series of 252 patients with septic shock, microvascular perfusion was an independent factor associated with survival.(3) Of note this is not an on-and-off but rather a progressive phenomenon....

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  • ...Recently, alterations in microcirculatory blood flow have been identified in severe sepsis(1) and the severity of these alterations is associated with a poor outcome.(2,3) The impact of therapeutic interventions on microcirculatory function is beginning to be reported....

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  • ...Interestingly, the severity of microvascular alterations was an independent factor associated with outcome in the early and later phases of sepsis, but the cut-off value separating survivors from non-survivors was lower in the early phase.(3) Although one may consider that the microcirculation is just adapting to direct cellular alterations, several factors suggest that microcirculatory alterations are the primary event leading to cellular dysfunction....

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  • ...2).(3) Looking at which variables differed between survivors and non-survivors, the proportion of perfused capillaries was the strongest predictor of outcome....

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References
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Journal ArticleDOI
TL;DR: The form and validation results of APACHE II, a severity of disease classification system that uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status, are presented.
Abstract: This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases. When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.

14,583 citations

Journal ArticleDOI
TL;DR: An update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008 is provided.
Abstract: Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

9,137 citations

Journal ArticleDOI
TL;DR: The ESICM developed a so-called sepsis-related organ failure assessment (SOFA) score to describe quantitatively and as objectively as possible the degree of organ dysfunction/failure over time in groups of patients or even in individual patients.
Abstract: Multiple organ failure (MOF) is a major cause of morbidity and mortali ty in the critically ill patient. Emerging in the 1970s, the concept of MOF was linked to modern developments in intensive care medicine [1]. Although an uncontrolled infection can lead to MOF [2], such a phenomenon is not always found. A number of mediators and the persistence of tissue hypoxia have been incriminated in the development of MOF [3]. The gut has been cited as a possible \"moto r \" of MOF [4]. Nevertheless, our knowledge regarding the pathophysiology of MOF remains limited. Furthermore, the development of new therapeutic interventions aiming at a reduction of the incidence and severity of organ failure calls for a better definition of the severity of organ dysfunction/failure to quantify the severity of illness. Accordingly, it is important to set some simple but objective criteria to define the degree of organ dysfunction/failure. The evolution of our knowledge of organ dysfunction/failure led us to establish several principles: 1. Organ dysfunction/failure is a process rather than an event. Hence, it should be seen as a continuum and should not be described simply as \"present\" or \"absent~' Hence, the assessment should be based on a scale. 2. The time factor is fundamental for several reasons: (a) Development and similarly resolution of organ failure may take some time. Patients dying early may not have time to develop organ dysfunction/failure. (b) The time course of organ dysfunction/failure can be mult imodal during a complex clinical course, what is sometimes referred to as a \"multiple-hit\" scenario. (c) Time evaluation allows a greater understanding of the disease process as a natural process or under the influence of therapeutic interventions. The collection of data on a daily basis seems adequate. 3. The evaluation of organ dysfunction/failure should be based on a limited number of simple but objective variables that are easily and routinely measured in every institution. The collection of this information should not impose any intervention beyond what is routinely performed in every ICU. The variables used should as much as possible be independent of therapy, since therapeutic management may vary from one institution to another and even from one patient to another (Table 1). Until recently, none of the existing systems describing organ failure met these criteria, since they were based on categorial definitions or described organ failure as present or absent [5-7] . The ESICM organized a consensus meeting in Paris in October 1994 to create a so-called sepsis-related organ failure assessment (SOFA) score, to describe quantitatively and as objectively as possible the degree of organ dysfunction/failure over time in groups of patients or even in individual patients (Fig. 1). There are two major applications of such a SOFA score: 1. To improve our Understanding of the natural history of organ dysfunction/failure and the interrelation between the failure of the various organs.

8,538 citations

Journal ArticleDOI
TL;DR: This document reflects a process whereby a group of experts and opinion leaders revisited the 1992 sepsis guidelines and found that apart from expanding the list of signs and symptoms of sepsi to reflect clinical bedside experience, no evidence exists to support a change to the definitions.
Abstract: Objective: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference", the goals of which were to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive inju- rious process that falls under the gen- eralized term 'sepsis' and includes sepsis-associated organ dysfunction as well. The general definitions intro- duced as a result of that conference have been widely used in practice, and have served as the foundation for in- clusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impe- tus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. Design: Several North American and European inten- sive care societies agreed to revisit the definitions for sepsis and related con- ditions. This conference was spon- sored by the Society of Critical Care Medicine (SCCM), The European So-

5,298 citations

Journal ArticleDOI
TL;DR: The form and validation results of APACHE II, a severity of disease classification system, are presented, showing an increasing score was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals.
Abstract: This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.

5,266 citations


"Microcirculatory alterations in pat..." refers methods in this paper

  • ...Acute Physiology and Chronic Health Evaluation II (APACHE II) (23) and Sequential Organ Failure Assessment (SOFA) (24) scores were computed at study inclusion....

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