Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016
St George's Hospital1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Hebron University6, University of Manitoba7, Emory University Hospital8, Hebrew University of Jerusalem9, Sunnybrook Health Sciences Centre10, University of Pittsburgh11, Saint Thomas - West Hospital12, University College London13, Vanderbilt University Medical Center14, Keio University15, Memorial Hospital of South Bend16, Cooper University Hospital17, University of Mississippi Medical Center18, Rush University Medical Center19, University of Ulsan20, Federal University of São Paulo21, Regions Hospital22, St. Michael's Hospital23, Washington University in St. Louis24, Ottawa Hospital25, University of Sydney26, Mount Sinai Hospital27, University of New South Wales28, Fujita Health University29, Christiana Care Health System30, Stanford University31, King Abdullah University of Science and Technology32, University of Kansas33, Harvard University34, California Pacific Medical Center35, University of Amsterdam36, Houston Methodist Hospital37
TL;DR: Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Abstract: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
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01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.
9,618 citations
TL;DR: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors.
Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many
6,968 citations
TL;DR: Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide.
4,124 citations
TL;DR: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications, and higher antICOagulation targets than in usual critically ill patients should therefore probably be suggested.
Abstract: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.
2,147 citations
Cites background from "Surviving Sepsis Campaign: Internat..."
...As is the case with sepsis, prophylactic anticoagulation of patients with severe COVID-19 may be recommended [6]....
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...Patients were managed following current guidelines [6] without specific therapeutic intervention....
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McMaster University1, Copenhagen University Hospital2, King Saud bin Abdulaziz University for Health Sciences3, Albert Einstein College of Medicine4, University of Toronto5, Rhode Island Hospital6, Brown University7, Utrecht University8, Oklahoma State University Center for Health Sciences9, NewYork–Presbyterian Hospital10, Peking Union Medical College Hospital11, Sunnybrook Health Sciences Centre12, Humanitas University13, University of Ulsan14, National Institutes of Health15, Imperial College London16, United Arab Emirates University17, Population Health Research Institute18, St George’s University Hospitals NHS Foundation Trust19, Emory University Hospital20, University at Buffalo21, Baylor College of Medicine22, University of Milano-Bicocca23, King Abdulaziz Medical City24, King Saud Medical City25, Royal North Shore Hospital26, The George Institute for Global Health27, University of Virginia28, University of Washington29
TL;DR: The Surviving Sepsis Campaign CO VID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19, and will provide new recommendations in further releases of these guidelines.
Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.
We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.
The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.
The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.
1,762 citations
Cites background or methods from "Surviving Sepsis Campaign: Internat..."
...Several professional societies have issued recommendations on the use of NMBAs in ARDS [100, [120] [121] [122] [123] ....
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...On the basis of the available body of evidence, several guidelines recommended using low Vt (4-8 mL/kg of predicted body weight) in patients with ARDS [99, 100] ....
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...A subsequent meta-analysis of RCTs comparing ventilatory strategies with low and high Pplat in patients with ARDS (15 studies) found that short-term mortality was higher in patients with Pplat > 32 cmH 2 [99, 100] ....
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References
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University College London1, The Feinstein Institute for Medical Research2, University of Pittsburgh3, Guy's and St Thomas' NHS Foundation Trust4, Monash University5, Vanderbilt University6, Emory University7, Washington University in St. Louis8, Brown University9, University of Toronto10, Sunnybrook Health Sciences Centre11
TL;DR: The task force concluded the term severe sepsis was redundant and 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 sepsi or at risk of developing sepsic shock.
Abstract: 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.
14,699 citations
TL;DR: The advantages of the GRADE system are explored, which is increasingly being adopted by organisations worldwide and which is often praised for its high level of consistency.
Abstract: Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide
13,324 citations
Additional excerpts
...GRADE (Grading of Recommendations Assessment, Development, and Evaluation) システムに従ってエビデンスレ ベルを「高い(high)」から「非常に低い(very low)」に分類し、また 推奨の強さも決定した (Table 1 and 2)(14)。GRADEシステムは 6つのカテゴリからエビデンスレベルを評価している。すなわち、 1研究の限界、2非一貫性、3非直接性、4不正確さ、5出版バイア ス、そして6その他で評価し、さらにその介入について、利益と害、 患者の価値観と好み、コストと資源、実現可能性と受容性のバラン スを評価する。ガイドラインの専門家集団によって最終的に形成 される推奨度はこれらの要素の評価に基づいている。GRADEに よるエビデンスレベルの定義をTable 1に示す。 RCTはまずは「高い(high-quality)エビデンスレベル」と評価し ておき、前述のカテゴリの制約によってダウングレードすること とした。一方で観察研究(非無作為化研究)は「低い(low-quality) エビデンスレベル」と評価しておき、その規模の大きさや他の要素 によってアップグレードすることとした。GRADEシステムでは 推奨度の強さを「強い(strong)」または「弱い(weak)」と分類する。 これらの決定に影響する要素を Table 2に示した。ガイドライン 委員会は、推奨を遵守することによる好ましい影響が好ましくな い影響を上回るかを評価し推奨度に反映させた。 「強い推奨」は推奨を遵守することで好ましい影響が明らかに好 ましくない影響を上回る、という委員会の意見を反映している。 「弱い推奨」は推奨を遵守することによる好ましい影響がおそらく 好ましくない影響を上回ると判断されているということを示して いるが、委員会はこの判断が確実ではないとみなしている。その理 由は利益と害に関し不確実性があり、エビデンスレベルが低いと 判断されていること、利益にも不利益にもなりえると判断される ことにある。強い推奨には「推奨する(we recommend)」と記述し、 弱い推奨には「提案する(we suggest)」と記述している。SSCG2012 年版では英数字を組み合わせた分類を用いていた。それを今回の 分類システムのものと比較したものをTable 3に示す。 ある推奨項目で「強い推奨(strong)」と呼ぶことは、ほとんどの 患者はその介入を受けるべきであり、ほとんどの臨床家はほとん どの状況でそれを使う、ということを含意している。個々の患者に とっての好ましさ、および臨床的な特性などによって強い推奨を 適応しにくい状況は存在しうる。それらをTable 4に示した。強い 推奨とは標準治療を意味するものではない。 ガイドライン全体を通して多くの「BPS(best practice statement、最 良の治療)」を提示している。これらの記載は分類されていないが強く 推奨されることを意味し、厳しい基準のもとに記載されている。たとえ ば、利益または害が明確であるが、エビデンスとしてまとめることが困 難なものや、GRADEシステムに適応しにくいものをBPSとして記載し ている。BPSとして指定する際には、Table 5に示しているGRADEワー キンググループによって提示された基準を適用している(15)。...
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...GRADE(Grading of Recommendations Assessment, Development, and Evaluation) システムに従ってエビデンスレ ベルを「高い(high)」から「非常に低い(very low)」に分類し、また 推奨の強さも決定した (Table 1 and 2)(14)。GRADEシステムは 6つのカテゴリからエビデンスレベルを評価している。すなわち、 1研究の限界 2 一貫 3非直接性 4不正確さ、5出版バイア ス、そして6その他で評価し、さらにその介入について、利益と害、 患者の価値観と好み、コストと資源、実現可能性と受容性のバラン スを評価する。ガイドラインの専門家集団によって最終的に形成 される推奨度はこれらの要素の評価に基づいている。GRADEに よるエビデンスレベルの定義をTable 1に示す。 RCTはまずは「高い(high-quality)エビデンスレベル」と評価し ておき、前述 カテゴリの制約によってダウングレードすること とした。一方で観察研究(非無作為化研究)は「低い(low-quality) エビデンスレベル」と評価しておき、その規模の大きさや他の要素 によってアップグレードすることとした。GRADEシステムでは 推奨度の強さを「強い(strong)」または「弱い(weak)」と分類する。 これらの決定に影響する要素を Table 2に示した。ガイドライン 委員会は、推奨を遵守す ことによる好ましい影響が好ましくな い影響を上回るかを評価し推奨度に反映させた。 「強い推奨」は推奨を遵守することで好ましい影響が明らかに好 ましくない影響を上回る、という委員会の意見を反映している。 「弱い推奨」は推奨を遵守することによる好ましい影響がおそらく 好ましくない影響を上回ると判断されているということを示して いるが、委員会はこの判断が確実ではないとみなしている。その理 由は利益と害に関し不確実性があり、エビデンスレベルが低いと 判断されていること、 不利益にもなりえると判断される ことにある。強い推奨には「推奨する(we recommend)」と記述し、 弱い推奨には「提案する(we suggest)」と記述している。SSCG2012 年版では英数字を組み合わせた分類を用いていた。それを今回の 分類システムのものと比較したものをTable 3に示す。 ある推奨項目で「強い推奨(strong)」と呼ぶことは、ほとんどの 患者はその介入を受けるべきであり、ほとんどの臨床家はほとん どの状況でそれを使う、ということを含意している。個々の患者に とっての好ましさ、および臨床的な特性などによって強い推奨を 適応しにくい状況は存在しうる。それらをTable 4に示した。強い 推奨とは標準治療を意味するものではない。 ガイドライン全体を通して多くの「BPS(best practice statement、最 良の治療)」を提示している。これらの記載は分類されていないが強く 推奨されることを意味し、厳しい基準のもとに記載されている。たとえ ば、利益または害 明確であるが、エビデンスとしてまとめることが困 難なものや、GRADEシステムに適応しにくいものをBPSとして記載し ている。BPSとして指定する際 は、Table 5に示しているGRADEワー キンググループによって提示された基準を適用している(15)。...
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TL;DR: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
Abstract: Background Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P Conclusions In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
11,028 citations
"Surviving Sepsis Campaign: Internat..." refers result in this paper
...The largest trial of a volume- and pressure-limited strategy showed 9% absolute decrease in mortality in ARDS patients ventilated with tidal volumes of 6 mL/kg compared with 12 mL/ kg PBW, and aiming for plateau pressure ≤ 30 cm H 2 O (350)....
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...These studies showed differing results, which may have been caused by differences in airway pressures in the treatment and control groups (347, 350, 352)....
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01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.
9,618 citations
Journal Article•
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TL;DR: A randomized controlled experiment is designed to test whether access to affordable day care (in the form of subsidies, for example) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired.
Abstract: This pilot aims to better understand the market for childcare in Saudi Arabia – both the supply and demand sides – and to design a randomized controlled experiment to test whether access to affordable day care (in the form of subsidies, for example) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired. In addition, the study seeks to understand the degree to which employment early on in one’s life impacts employment in later stages. The pilot will provide information on the groups of women the experiment should target, appropriate levels for the childcare subsidy, and the quality and current geographic locations of daycare sites. Expected Impact Determine the effects of facilitating childcare access on Saudi women’s employment. PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Peck
9,609 citations