https://journal.chestnet.org/article/S0012-3692(16)38415-X/pdf

Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis

The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.

Acute respiratory distress syndrome: the Berlin Definition.

Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

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Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

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

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-

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference

The association between body mass index and clinical outcomes in acute lung injury.

Rationale: Prior studies supported an association between intensive care unit (ICU) organizational model or staffing patterns and outcome in critically ill patients. Objectives: To examine the association of closed versus open models with patient mortality across adult ICUs in King County (WA). Methods: Cohort study of patients with acute lung injury (ALI). Measurements and Main Results: ICU structure, organization, and patient care practices were assessed using self-administered mail questionnairescompletedbythemedicaldirectorandnursemanager. We defined closed ICUs as units that required patient transfer to ormandatorypatientcomanagementbyanintensivistandopenICUs as those relying on other organizational models. Outcomes were obtained from the King County Lung Injury Project, a populationbased cohort of patients with ALI. The main endpoint was hospital mortality. Of 24 eligible ICUs, 13 ICUs were designated closed and 11 open. Completesurvey datawere available for 23(96%)ICUs. Higher physician and nurse availability was reported in closed versus open ICUs. A total of684of1,075 (63%) ofpatientswith ALI werecared for inclosedICUs.Afteradjustingforpotentialconfounders,patientswith ALI cared for in closed ICUs had reduced hospital mortality (adjusted odds ratio, 0.68; 95% confidence interval, 0.53, 0.89; P 5 0.004). ConsultationbyapulmonologistinopenICUswasnotassociatedwith improved mortality (adjusted odds ratio, 0.94; 95% confidence interval, 0.74, 1.20; P 5 0.62). These findings were robust for varying assumptions about the study population definition. Conclusions: Patients with ALI cared for in a closed-model ICU have reduced mortality. These data support recommendations to implement structured intensive care in the United States.

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Effect of intensive care unit organizational model and structure on outcomes in patients with acute lung injury

The acute respiratory distress syndrome (ARDS) frequently results in a fibroproliferative response that precludes effective alveolar repair. Transforming growth factor-alpha (TGF-alpha), a potent epithelial and mesenchymal cell mitogen, may modulate the response to lung injury. In this study, we determined whether bronchoalveolar lavage fluid (BALF) concentrations of TGF-alpha are increased during the first 2 wk after the onset of ARDS and, if so, whether increased TGF-alpha levels in lavage fluid are associated with increased levels of procollagen peptide III (PCP III), a biological marker of fibroproliferation, and with increased fatality rates. We enrolled 74 consecutive patients with ARDS prospectively identified on admission to the intensive care unit of a tertiary care hospital, and 11 patients with chronic interstitial lung disease. Thirteen healthy volunteers served as control subjects. TGF-alpha concentrations were measured in BALF recovered on Days 3, 7, and 14 after the onset of ARDS (total of 130 lavage samples). TGF-alpha was detected in the lavage fluid of 90% of patients with ARDS (67 of 74), and in 100% of patients with idiopathic pulmonary fibrosis (IPF) (10 of 10), but in none of 13 normal volunteers. At each day tested, the median lavage TGF-alpha level of patients with ARDS was significantly higher than that of normals. The overall fatality rate was 45% (33 of 74 patients). In a univariate analysis, the median TGF-alpha levels in nonsurvivors were 1.5-fold higher at Day 7 (p = 0.06) and 1.8-fold higher at Day 14 (p = 0.048). The fatality rate was 4 times higher (CI 1.6, 17.5) for patients with both increased lavage TGF-alpha and PCP III concentrations at Day 7 than for patients with low TGF-alpha and PCP III values, indicating a synergistic relationship between TGF-alpha and PCP III. We conclude that increased levels of TGF-alpha in BALF are common in patients with ARDS and that lavage TGF-alpha is associated with a marker of the fibroproliferative response in sustained ARDS.

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Elevated Transforming Growth Factor- α Levels in Bronchoalveolar Lavage Fluid of Patients with Acute Respiratory Distress Syndrome

Objective: Studies describing predictors of mortality in patients with acute lung injury were primarily derived from selected academic centers. We sought to determine the predictors of mortality in a population-based cohort of patients with acute lung injury and to characterize the performance of current severity of illness scores in this population. Design: Secondary analysis of a prospective, multicenter, population-based cohort. Setting: Twenty-one hospitals in Washington State. Patients: The cohort included 1,113 patients with acute lung injury identified during the year 1999 –2000. Interventions: None. Measurements and Main Results: We evaluated physiology, comorbidities, risk factors for acute lung injury, and other variables for their association with death at hospital discharge. Bivariate predictors of death were entered into a multiple logistic regression model. We compared Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, and Simplified Acute Physiology Score II to the multivariable model using area under the receiver operating characteristic curve. The model was validated in an independent cohort of 886 patients with acute lung injury. Modified acute physiology score, age, comorbidities, arterial pH, minute ventilation, PaCO2 ,P a O2/FIO2 ratio, intensive care unit admission source, and intensive care unit days before onset of acute lung injury were independently predictive of in-hospital death (p < .05). The area under the receiver operating characteristic curve for the multivariable model was superior to that of APACHE III (.81 vs. .77, p < .001) but was no different after external validation (.71 vs. .70, p .64). Conclusions: The predictors of mortality in patients with acute lung injury are similar to those predictive of mortality in the general intensive care unit population, indicating disease heterogeneity within this cohort. Accordingly, APACHE III predicts mortality in acute lung injury as well as a model using variables selected specifically for patients with acute lung injury. (Crit Care Med 2008; 36:1412–1420)

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Predictors of hospital mortality in a population-based cohort of patients with acute lung injury.

Objectives
To determine the incidence and outcomes of intensive care unit-acquired neuromyopathy and to investigate the role of methylprednisolone in survivors of persistent acute lung injury.

/pdf/intensive-care-unit-acquired-neuromyopathy-and-4vleh0r7dd.pdf

Leonard D. Hudson

Papers

The association between body mass index and clinical outcomes in acute lung injury.

Effect of intensive care unit organizational model and structure on outcomes in patients with acute lung injury

Elevated Transforming Growth Factor- α Levels in Bronchoalveolar Lavage Fluid of Patients with Acute Respiratory Distress Syndrome

Predictors of hospital mortality in a population-based cohort of patients with acute lung injury.

Intensive care unit-acquired neuromyopathy and corticosteroids in survivors of persistent ARDS.