Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial
Complutense University of Madrid1, Hospital General Universitario Gregorio Marañón2, Katholieke Universiteit Leuven3, Royal Free Hospital4, University of Alcalá5, Martin Luther University of Halle-Wittenberg6, University of Paris-Sud7, French Institute of Health and Medical Research8, University of Bonn9, University of Rostock10, Charité11, University of Barcelona12, University of Cambridge13, University of Zurich14, Foundation for Liver Research15
TL;DR: At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated, however, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE.
About: This article is published in Hepatology.The article was published on 2013-03-01 and is currently open access. It has received 437 citations till now. The article focuses on the topics: Population & Alcoholic hepatitis.
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TL;DR: The panel of experts, having emphasised the importance of initiating aetiologic treatment for any degree of hepatic disease at the earliest possible stage, extended its work to all the complications of cirrhosis which had not been covered by the European Association for the Study of the Liver guidelines.
1,534 citations
Cites methods or result from "Extracorporeal albumin dialysis wit..."
...Both methods have been evaluated in large RCTs in patients with ACLF and no significant effects on survival could be demonstrated.(388,389) It should be emphasised however, that the definition of ACLF in both trials was different than the current definition of ACLF based on the CANONIC study....
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...In two controlled studies, both the socalled artificial liver support systems, either the molecular adsorbents recirculating system (MARS ) or Prometheus , showed promising beneficial effects in patients with type 1 HRS, but should be further investigated.(388,389)...
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University of Delhi1, University of New South Wales2, Post Graduate Institute of Medical Education and Research3, University of Hong Kong4, University of Kelaniya5, The Aga Khan University Hospital6, University College London7, Chulalongkorn University8, Capital Medical University9, University of Malaya10, Huazhong University of Science and Technology11, Bangabandhu Sheikh Mujib Medical University12, French Institute of Health and Medical Research13, Jaslok Hospital14, Iwate Medical University15, Gleneagles Hospital16
TL;DR: The original proposed definition of ACLF was found to withstand the test of time and identify a homogenous group of patients presenting with liver failure, which led to the development of the final AARC consensus.
Abstract: The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia–Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22–23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.
1,125 citations
Cites background from "Extracorporeal albumin dialysis wit..."
..., HELIOS (for Prometheus) [125] and RELIEF trial (for MARS) [124], that failed to show any benefit with these modalities on short-term transplant-free survival,...
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...These results have been substantiated by the recently published two large European randomized multicentric controlled trials, i.e., HELIOS (for Prometheus) [125] and RELIEF trial (for MARS) [124], that failed to show any benefit with these modalities on short-term transplant-free survival, which was the primary end point of these studies....
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...In the most recent meta-analysis and systematic review, no benefit of MARS treatment in reducing mortality as compared to SMT was noted [130], even though both these meta-analysis have the limitations of enrolling a heterogenous group of patients....
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TL;DR: In this paper, the authors focus on the current understanding of acute-on-chronic liver failure from the clinical, prognostic and pathophysiological perspectives and indicate potential biomarkers and therapeutic targets for intervention.
648 citations
TL;DR: The latest data on the treatment and management of alcohol-related liver disease will be reviewed and up to date recommendations for clinical management will be provided.
476 citations
TL;DR: Assessment of ACLF patients at 3‐7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility.
470 citations
Cites background from "Extracorporeal albumin dialysis wit..."
...Median delay between ACLF diagnosis and LT was 11 (1-28) days....
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...Median time between initial and last ACLF grade assessment was 14 (1-28) days....
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References
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Cooper University Hospital1, St George's Hospital2, Memorial Hospital of Rhode Island3, Emory University4, University of Colorado Denver5, McMaster University6, Washington University in St. Louis7, University of Chicago8, University of Jena9, Rush University Medical Center10, University of Pittsburgh11, University of Pennsylvania12, Federal University of São Paulo13, University of Toronto14, Royal Perth Hospital15, Guy's and St Thomas' NHS Foundation Trust16, Université libre de Bruxelles17
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
TL;DR: This study randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit.
Abstract: Background Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. Methods We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. Results Of the 263 enrolled patients, 130 were ...
8,811 citations
"Extracorporeal albumin dialysis wit..." refers background in this paper
...Length of hospital stay was similar in both groups (SMT median [range]: 23 [1-28]; MARS median [range]: 24 [2-28] days) as well as the proportion of patients undergoing mechanical ventilation at any time during hospitalization (SMT 21....
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TL;DR: The MELD scale is a reliable measure of mortality risk in patients with end‐stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities in patient groups with a broader range of disease severity and etiology.
4,184 citations
"Extracorporeal albumin dialysis wit..." refers background in this paper
...Length of hospital stay was similar in both groups (SMT median [range]: 23 [1-28]; MARS median [range]: 24 [2-28] days) as well as the proportion of patients undergoing mechanical ventilation at any time during hospitalization (SMT 21....
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Cooper University Hospital1, Rhode Island Hospital2, University of Birmingham3, Stony Brook University4, McMaster University5, University of Jena6, University of Pittsburgh7, St Thomas' Hospital8, University Hospital of Lausanne9, University of Minnesota10, St. Michael's Hospital11, University of Turin12, University of Hertfordshire13, Johns Hopkins University School of Medicine14, Harvard University15, NorthShore University HealthSystem16, Houston Methodist Hospital17
TL;DR: In this paper, the authors provide an update to the original Surviving Sepsis Campaign clinical management guidelines for management of severe sepsis and septic shock, published in 2004.
Abstract: 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.
3,928 citations
01 Jan 2008
TL;DR: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, the GRADE system was used to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations.
Abstract: 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. 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. 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. 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). 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.
3,824 citations