Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

https://jamanetwork.com/journals/jama/articlepdf/2492881/jsc160002.pdf

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Context Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. Objective To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. Design, Setting, and Patients The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14 414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13 796 adult (>18 years) patients. Results On the day of the study, 7087 of 13 796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [ 682/6352], respectively; P  Conclusions Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.

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International Study of the Prevalence and Outcomes of Infection in Intensive Care Units

Objective:To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units.Design:Cohort, multiple-center, observational study.Setting:One hundred and ninety-eight intensive care units in 24 European countries.Patients:All new adult admissi

Sepsis in European intensive care units: results of the SOAP study.

Objective: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. Conclusions: The Task Force recommends that initial biochemical testing for PPGLs shou...

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Pheochromocytoma and paraganglioma: An endocrine society clinical practice guideline

The mixed venous-to-arterial carbon dioxide (CO2) tension difference [P (v-a) CO2] is the difference between carbon dioxide tension (PCO2) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO2 in arterial blood. P (v-a) CO2 depends on the cardiac output and the global CO2 production, and on the complex relationship between PCO2 and CO2 content. Experimental and clinical studies support the evidence that P (v-a) CO2 cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO2 generated by the peripheral tissues. P (v-a) CO2 can be replaced by the central venous-to-arterial CO2 difference (ΔPCO2), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the ΔPCO2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO2) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased ΔPCO2 (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the ΔPCO2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO2 production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO2 related to metabolic demand. The combination of P (v-a) CO2 or ΔPCO2 with oxygen-derived parameters through the calculation of the P (v-a) CO2 or ΔPCO2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.

https://hal.univ-lille.fr/hal-02613556/document

Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock.

Background: Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. Methods: The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. Results: The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86– * Associate Professor, Department of Anesthesiology & Perioperative Care, School of Medicine, University of California, Irvine, Irvine, California. † Associate Professor, Department of Anesthesiology and Critical Care Medicine, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France, and Centre for Statistics in Medicine, Wolfson College, University of Oxford, Oxford, United Kingdom. ‡ Associate Professor, Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital, Zurich, Switzerland. § Associate Professor, Department of Anesthesiology and Critical Care Medicine, Centre Hospitalier Universitaire Pitié-Salpêtrière. Professor, Department of Anesthesiology and Critical Care, Hôpital Louis Pradel, Lyon, France. # Professor, Department of Anesthesiology and Critical Care Medicine, Centre Hospitalier Universitaire de Lille, Lille, France. Received from the Department of Anesthesiology & Perioperative Care, School of Medicine, University of California, Irvine, Irvine, California. Submitted for publication December 7, 2010. Accepted for publication May 6, 2011. Support was provided solely from institutional and/or departmental sources. Dr. Cannesson is a consultant for Edwards Lifesciences (Irvine, California), Covidien (Boulder, Colorado), Masimo Corp. (Irvine, California), ConMed (Irvine, California), Philips Medical System (Suresnes, France), CNsystem (Vienna, Austria), BMeye (Amsterdam, The Netherlands), and Fresenius Kabi (Sèvres, France). Dr. Le Manach is a consultant for Air Liquide Santé (Paris, France) and received lecture/travel fees from Masimo Corp. and Fresenius Kabi. Dr. Hofer is a consultant for Pulsion Medical Systems (Munchen, Germany), Edwards Lifesciences, and CSL Behring (King of Prussia, Pennsylvania). Dr. Vallet received lecture/travel fees from Masimo Corp., Edwards Lifesciences, Fresenius Kabi, and Baxter Corp. (Deerfield, Illinois). Dr. Tavernier received lecture/travel fees from Masimo Corp. and Fresenius Kabi. Address correspondence to Dr. Cannesson: Department of Anesthesiology and Perioperative Care, University of California, Irvine, 333 City Boulevard West Side, Orange, California 92868-3301. maxime_ cannesson@hotmail.com. This article may be accessed for personal use at no charge through the Journal Web site, www.anesthesiology.org. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2011; 115:231–41 What We Already Know about This Topic • Applying a gray zone statistical approach to decision-making may increase the utility of diagnostic measures, including pulse pressure variation to predict fluid responsiveness What This Article Tells Us That Is New • Despite a strong predictive value, the gray zone approach applied to pulse pressure variation may be inconclusive in approximately 25% of patients for prediction of fluid responsiveness in mechanically ventilated patients during general anesthesia This article is accompanied by an Editorial View. Please see: De Hert SG: Assessment of fluid responsiveness: Insights in a “gray zone.” ANESTHESIOLOGY 2011; 115:229–30. Anesthesiology, V 115 • No 2 August 2011 231 Downloaded From: http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?url=/data/journals/jasa/931110/ on 01/03/2019 0.92) for PPV, compared with 0.57 (95% CI: 0.54–0.59) for central venous pressure (P 10 ). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. Conclusion: Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia. D YNAMIC variables relying on cardiopulmonary interactions have been shown to be the best predictors of fluid responsiveness in patients during general anesthesia and mechanical ventilation. Today, these variables can be continuously monitored using dedicated devices and they can be derived noninvasively from the pulse oximeter waveform. Several studies have suggested that these variables could be used for intraoperative goal-directed fluid management and that this approach may have a beneficial impact on patients’ outcome in terms of a reduction in postoperative complications resulting in a decrease in length of hospital stay. Thus far, studies evaluating the ability of respiratory arterial pulse pressure variations (PPV) to predict fluid responsiveness have been conducted in small samples of selected patient groups from single centers, using a receiver operating characteristic (ROC) curve approach. However, most quantitative tests do not perfectly discriminate between subjects with and without a given status (i.e., fluid responder or nonresponder in the current case), and their results do not allow certainty in the determination of this status for screening purposes. The “gray zone” approach has been proposed to avoid the binary constraint of a “black-or-white” decision of the ROC curve approach that often does not fit the reality of clinical or screening practice. The gray zone technique proposes two cutoffs that constitute the borders of the gray zone. The first cutoff allows exclusion of the diagnosis (fluid responsiveness in the current case) with near certainty (i.e., privilege sensitivity and negative predictive value), whereas the second cutoff is chosen to include the diagnosis with near certainty (i.e., privilege specificity and positive predictive value). Intermediate values included in the gray zone correspond to a prediction not precise enough for diagnostic decision. A second potential limitation of the ROC curve analysis for evaluation of dynamic variables is that most previous studies indicate it necessitates a fixed definition of fluid responsiveness (an increase of more than 10% or 15% in stroke volume [SV] or cardiac output [CO]) after a 250or 500-ml fluid challenge, whereas according to the FrankStarling curve, the response to a given volume load is actually a continuum of values ranging from “no increase” (or even a decrease) to a “large increase” in SV and/or CO. In addition, the benefit-risk balance of fluid administration may vary between patients, and this has never been taken into account in previous analyses of prediction of fluid responsiveness. The application of these approaches to a large population of patients would allow knowing: (1) the proportion of cases within the gray zone, (2) the range of changes in SV or CO that can be expected in these patients when a fluid challenge is presented, and (3) refinement of the definition of thresholds that should be used for PPV-guided management protocols. Thus, the aim of our study was to assess the diagnostic accuracy of PPV for prediction of fluid responsiveness in a large, multicenter study of mixed groups of patients in the perioperative period and to express its predictive value using a gray zone approach. We also studied the impact of fluid responsiveness definition and a model for benefit-risk assessment of fluid administration on the predictive value of PPV. Materials and Methods Institutional review board (Comité de Protection des Personnes Hospices Civils de Lyon, Lyon, France; Comité de Protection des Personnes Paris-Ile de France, France; Comité de Protection des Personnes Nord Ouest, Lille, France; and Institutional Review Board, Triemli City Hospital, Zurich, Switzerland) approvals were obtained. Patients were included either as part of clinical trials (for whom written and informed consents were obtained) or as part of routine clinical care (for whom no randomization and only routine care was performed, so waived informed consent was authorized). Data Collection Four European institutions (Hôpital Louis Pradel, Lyon, France; Hôpital La Pitié-Salpêtrière, Paris, France; Triemli City Hospital, Zurich, Switzerland; and Centre Hospitalier Universitaire de Lille, Lille, France) participated in this study. We defined preload responsiveness evaluation as an intravenous volume load of 500 ml colloid solution given over 10–20 min, immediately preceded and followed (2–5 min later) by hemodynamic measurements, including PPV and CO (or SV), performed with the aim of measuring the change in CO (or SV) induced by volume expansion. Each investigator collected every sequence of preload responsiveness evaluation that was prospectively recorded and available in his own database, provided that (1) the patient was an adult, with no history of arrhythmia, right ventricular failure, valvular heart disease, or intracardiac shunt, (2) he was undergoing general anesthesia, muscle paralysis, and mechanical ventilation in the controlled volume mode, (3) measurements and volume loading were performed in the operati

Assessing the Diagnostic Accuracy of Pulse Pressure Variations for the Prediction of Fluid Responsiveness: The “Gray Zone” Approach

OBJECTIVE To test the hypothesis that saline solution plus dobutamine increases gastrointestinal mucosal perfusion better than saline solution alone in a model of endotoxic shock. DESIGN Prospective, randomized, unblinded study. SETTING Animal research laboratory affiliated with a university teaching hospital. SUBJECTS Twelve female pigs, weighing 30 to 32 kg. INTERVENTIONS Animals were anesthetized, and their lungs were mechanically ventilated. Catheters were inserted into the right atrium, pulmonary artery, and carotid artery for blood sampling and blood pressure and cardiac output measurements. A tonometer and a laser Doppler probe were placed in the lumen of the stomach and the ileum for determination of mucosal acid-base status and measurement of mucosal blood flow. Group 1 animals (n = 6) received an infusion (T = 0 min) of 150 mcirog/kg Escherichia coli endotoxin and normal saline solution (0.3 mL/kg/min). Group 2 animals (n = 6) received an infusion of endotoxin and were resuscitated with the same method as used in group 1, but an infusion of dobutamine (5 microg/kg/min) was begun at T = 60 mins, and continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS Both experimental regimens produced shock, with decreased mean arterial pressure and systemic vascular resistance, without change in cardiac output and oxygen delivery. Endotoxin plus saline infusion decreased gastrointestinal mucosal blood flow to <60% of baseline and decreased gastrointestinal pH. In contrast, gastrointestinal mucosal blood flow returned to baseline values, and intramucosal pH tended to normalize by the end of the saline solution plus dobutamine resuscitative protocol. CONCLUSION Compared with saline solution alone, saline solution plus dobutamine increased blood flow to the gastrointestinal mucosa, and may have partially improved oxygenation.

Dobutamine improves gastrointestinal mucosal blood flow in a porcine model of endotoxic shock.

The vascular endothelium is a highly specialized tissue involved in modulating immune responses and vascular cell growth, and in regulating the level of hemostatic, inflammatory, and vasoactive agents in the blood (Table 1). Endothelial cells line vessels in every organ system and regulate the flow of nutrient substances, diverse biologically active molecules, and the blood cells themselves. This ‘gate-keeping’ role of the endothelium is effected through the presence of membrane-bound receptors for numerous molecules including proteins, lipid transporting particles, metabolites and hormones, as well as through specific junction proteins and receptors that govern cell-to-cell and cell-tomatrix interactions [1]. This feature explains why endothelium dysfunction and/or injury with subendothelium exposure facilitates leukocyte and platelet aggregation and aggravation of coagulopathy. Therefore, endothelial dysfunction and/or injury should favor impaired perfusion, tissue hypoxia and subsequent organ dysfunction.

Endothelial Cell Dysfunction and Abnormal Tissue Perfusion

Venous oxygen saturation is a clinical tool which integrates the whole body oxygen uptake-to-delivery (VO2-DO2) relationship. In the clinical setting, in the absence of pulmonary artery catheter (PAC)-derived mixed venous oxygen saturation (SvO2), the central venous oxygen saturation (ScvO2) is increasingly being used as a reasonably accurate surrogate [1]. Central venous catheters (CVCs) are simpler to insert, and generally safer and cheaper than PACs. The CVC allows sampling of blood for measurement of ScvO2 or even continuous monitoring if an oximetry catheter is being used. The normal range for SvO2 is 68 to 77 % and ScvO2 is considered to be 5 % above these values [2].

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Benoit Vallet

Papers

Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock.

Assessing the Diagnostic Accuracy of Pulse Pressure Variations for the Prediction of Fluid Responsiveness: The “Gray Zone” Approach

Dobutamine improves gastrointestinal mucosal blood flow in a porcine model of endotoxic shock.

Endothelial Cell Dysfunction and Abnormal Tissue Perfusion

Venous oxygen saturation as a physiologic transfusion trigger