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Kaya E, Nekarda P, Traut I, Aurich P, Canbay A, Katsounas A. [When should a liver disease patient be admitted to the intensive care unit?]. Med Klin Intensivmed Notfmed 2024; 119:470-477. [PMID: 39017943 DOI: 10.1007/s00063-024-01160-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 05/27/2024] [Accepted: 06/04/2024] [Indexed: 07/18/2024]
Abstract
Liver diseases are a significant global cause of morbidity and mortality. Liver cirrhosis can result in severe complications such as bleeding, hepatic encephalopathy (HE), and infections. Implementing a clear strategy for intensive care unit (ICU) admission management improves patient outcomes. Hemodynamically significant esophageal/gastric variceal bleeding (E/GVB) and grade 4 HE, when accompanied by the need for renal replacement therapy (RRT), are definitive indications for ICU admission. E/GVB, spontaneous bacterial peritonitis (SBP), and infections with multidrug-resistant organisms (MDRO) require close and stringent critical assessment. Patients with severe hepatorenal syndrome (HRS) or respiratory failure have increased baseline mortality and most likely benefit from early ICU treatment. Rapid identification of sepsis in patients with liver cirrhosis is a crucial criterion for ICU admission. Prioritizing cases based on mortality risk and clinical urgency enables efficient resource utilization and optimizes patient management. In addition, "Liver Units" provide an intermediate care (IMC) level for patients with liver diseases who require close monitoring but do not need immediate intensive care.
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Affiliation(s)
- Eda Kaya
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Patrick Nekarda
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Isabella Traut
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Philipp Aurich
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Ali Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Antonios Katsounas
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland.
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de Haan J, Termorshuizen F, de Keizer N, Gommers D, Hoed CD. One-year transplant-free survival following hospital discharge after ICU admission for ACLF in the Netherlands. J Hepatol 2024; 81:238-247. [PMID: 38479613 DOI: 10.1016/j.jhep.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND & AIMS Patients with acute decompensation of cirrhosis or acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. Existing research, mostly from specialized liver transplant centers, largely addresses short-term outcomes. Our aim was to evaluate in-hospital mortality and 1-year transplant-free survival after hospital discharge in the Netherlands. METHODS We conducted a nationwide observational cohort study, including patients with a history of cirrhosis or first complications of cirrhotic portal hypertension admitted to ICUs in the Netherlands between 2012 and 2020. The influence of ACLF grade at ICU admission on 1-year transplant-free survival after hospital discharge among hospital survivors was evaluated using unadjusted Kaplan-Meier survival curves and an adjusted Cox proportional hazard model. RESULTS Out of the 3,035 patients, 1,819 (59.9%) had ACLF-3. 1,420 patients (46.8%) survived hospitalization after ICU admission. The overall probability of 1-year transplant-free survival after hospital discharge was 0.61 (95% CI 0.59-0.64). This rate varied with ACLF grade at ICU admission, being highest in patients without ACLF (0.71; 95% CI 0.66-0.76) and lowest in those with ACLF-3 (0.53 [95% CI 0.49-0.58]) (log-rank p <0.0001). However, after adjusting for age, malignancy status and MELD score, ACLF grade at ICU admission was not associated with an increased risk of liver transplantation or death within 1 year after hospital discharge. CONCLUSION In this nationwide cohort study, ACLF grade at ICU admission did not independently affect 1-year transplant-free survival after hospital discharge. Instead, age, presence of malignancy and the severity of liver disease played a more prominent role in influencing transplant-free survival after hospital discharge. IMPACT AND IMPLICATIONS Patients with acute-on-chronic liver failure often require intensive care unit (ICU) admission for organ support. In these patients, short-term mortality is high, but long-term outcomes of survivors remain unknown. Using a large nationwide cohort of ICU patients, we discovered that the severity of acute-on-chronic liver failure at ICU admission does not influence 1-year transplant-free survival after hospital discharge. Instead, age, malignancy status and overall severity of liver disease are more critical factors in determining their long-term survival.
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Affiliation(s)
- Jubi de Haan
- Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Fabian Termorshuizen
- National Intensive Care Evaluation (NICE) Foundation, Amsterdam, the Netherlands; Department of Medical Informatics, Amsterdam Public Health Institute, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Nicolette de Keizer
- National Intensive Care Evaluation (NICE) Foundation, Amsterdam, the Netherlands; Department of Medical Informatics, Amsterdam Public Health Institute, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Diederik Gommers
- Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Caroline den Hoed
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
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Goble SR, Ismail AS, Debes JD, Leventhal TM. Critical care outcomes in decompensated cirrhosis: a United States national inpatient sample cross-sectional study. Crit Care 2024; 28:150. [PMID: 38715040 PMCID: PMC11077702 DOI: 10.1186/s13054-024-04938-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 04/30/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Prior assessments of critical care outcomes in patients with cirrhosis have shown conflicting results. We aimed to provide nationwide generalizable results of critical care outcomes in patients with decompensated cirrhosis. METHODS This is a retrospective study using the National Inpatient Sample from 2016 to 2019. Adults with cirrhosis who required respiratory intubation, central venous catheter placement or both (n = 12,945) with principal diagnoses including: esophageal variceal hemorrhage (EVH, 24%), hepatic encephalopathy (58%), hepatorenal syndrome (HRS, 14%) or spontaneous bacterial peritonitis (4%) were included. A comparison cohort of patients without cirrhosis requiring intubation or central line placement for any principal diagnosis was included. RESULTS Those with cirrhosis were younger (mean 58 vs. 63 years, p < 0.001) and more likely to be male (62% vs. 54%, p < 0.001). In-hospital mortality was higher in the cirrhosis cohort (33.1% vs. 26.6%, p < 0.001) and ranged from 26.7% in EVH to 50.6% HRS. Mortality when renal replacement therapy was utilized (n = 1580, 12.2%) was 46.5% in the cirrhosis cohort, compared to 32.3% in other hospitalizations (p < 0.001), and was lowest in EVH (25.7%) and highest in HRS (51.5%). Mortality when cardiopulmonary resuscitation was used was increased in the cirrhosis cohort (88.0% vs. 72.1%, p < 0.001) and highest in HRS (95.7%). CONCLUSIONS One-third of patients with cirrhosis requiring critical care did not survive to discharge in this U.S. nationwide assessment. While outcomes were worse than in patients without cirrhosis, the results do suggest better outcomes compared to previous studies.
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Affiliation(s)
- Spencer R Goble
- Department of Medicine, Hennepin Healthcare, 730 South 8th Street, Minneapolis, MN, 55415, USA.
| | - Abdellatif S Ismail
- Department of Internal Medicine, University of Maryland Medical Center Midtown Campus, 827 Linden Ave, Baltimore, MD, 21201, USA
| | - Jose D Debes
- Department of Medicine, University of Minnesota, Mayo Memorial Building, MMC 250, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA
| | - Thomas M Leventhal
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, MMC 36, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA
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Mita A, Shimizu S, Ichiyama T, Yamamoto T, Yamaguchi A, Sonoda K, Mori K, Yamada T, Nakamura H, Imamura H. Outcomes of critically ill patients with liver failure who require mechanical ventilation: A retrospective, single-center study. Health Sci Rep 2024; 7:e1926. [PMID: 38469112 PMCID: PMC10925802 DOI: 10.1002/hsr2.1926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 11/28/2023] [Accepted: 02/03/2024] [Indexed: 03/13/2024] Open
Abstract
Background and Aims Critically ill patients with liver failure have high mortality. Besides the management of organ-specific complications, liver transplantation constitutes a definitive treatment. However, clinicians may hesitate to introduce mechanical ventilation for patients on liver transplantation waitlists because of poor prognosis. This study investigated the outcomes of intensive care and ventilation support therapy effects in patients with liver failure. Methods This single-center study retrospectively enrolled 32 consecutive patients with liver failure who were admitted to the intensive care unit from January 2014 to December 2020. The medical records were reviewed and analyzed retrospectively for Acute Physiologic and Chronic Health Evaluation (APACHE)-II. The model for end-stage liver disease scores, 90-day mortality, and survival was assessed using the Kaplan-Meier method. Results The average patient age was 45.5 ± 20.1 years, and 53% of patients were women. On intensive care unit admission, APACHE-II and model for end-stage liver disease scores were 20 and 28, respectively. Among 13 patients considered for liver transplantation, 4 received transplants. Thirteen patients (40.6%) were intubated and mechanically ventilated in the intensive care unit. The 90-day mortality rate of patients with and without mechanical ventilation in the intensive care unit (13, 61.5% vs. 19, 47.4%, p = 0.4905) was similar. APACHE-II score >21 was an independent predictor of mechanical ventilation requirement in patients with liver failure during intensive care unit stay. Conclusion Although critically ill patients with liver failure are at risk of multiorgan failure with poor outcomes, mechanical ventilation did not negatively affect the 90-day mortality or performance rates of liver transplantation. Clinicians should consider mechanical ventilation-based life support in critically ill patients with liver failure who are awaiting liver transplantation.
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Affiliation(s)
- Atsuyoshi Mita
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Sari Shimizu
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Takashi Ichiyama
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Takateru Yamamoto
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Akinori Yamaguchi
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Kosuke Sonoda
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Kotaro Mori
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Tomokatsu Yamada
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Hiroyuki Nakamura
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
| | - Hiroshi Imamura
- Intensive Care Unit, Shinshu University HospitalShinshu University School of MedicineMatsumotoJapan
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Harden Waibel B, Kamien AJ. Resuscitation and Preparation of the Emergency General Surgery Patient. Surg Clin North Am 2023; 103:1061-1084. [PMID: 37838456 DOI: 10.1016/j.suc.2023.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2023]
Abstract
Traditionally, the workflow surrounding a general surgery patient allows for a period of evaluation and optimization of underlying medical issues to allow for risk modification; however, in the emergency, this optimization period is largely condensed because of its time-dependent nature. Because the lack of optimization can lead to complications, the ability to rapidly resuscitate the patient, proceed to procedural intervention to control the situation, and manage common medical comorbidities is paramount. This article provides an overview on these subjects.
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Affiliation(s)
- Brett Harden Waibel
- Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198-3280, USA.
| | - Andrew James Kamien
- Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198-3280, USA
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Crocombe D, O’Brien A. Antimicrobial prophylaxis in decompensated cirrhosis: friend or foe? Hepatol Commun 2023; 7:e0228. [PMID: 37655979 PMCID: PMC10476838 DOI: 10.1097/hc9.0000000000000228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 06/21/2023] [Indexed: 09/02/2023] Open
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Perricone G, Artzner T, De Martin E, Jalan R, Wendon J, Carbone M. Intensive care management of acute-on-chronic liver failure. Intensive Care Med 2023; 49:903-921. [PMID: 37552333 DOI: 10.1007/s00134-023-07149-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/21/2023] [Indexed: 08/09/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome defined by an acute deterioration of the liver function associated with extrahepatic organ failures requiring intensive care support and associated with a high short-term mortality. ACLF has emerged as a major cause of mortality in patients with cirrhosis and chronic liver disease. ACLF has a unique pathophysiology in which systemic inflammation plays a key role; this provides the basis of novel therapies, several of which are now in clinical trials. Intensive care unit (ICU) therapy parallels that applied in the general ICU population in some organ failures but has peculiar differential characteristics in others. Critical care management strategies and the option of liver transplantation (LT) should be balanced with futility considerations in those with a poor prognosis. Nowadays, LT is the only life-saving treatment that can radically improve the long-term prognosis of patients with ACLF. This narrative review will provide insights on the current understanding of ACLF with emphasis on intensive care management.
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Affiliation(s)
- Giovanni Perricone
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy.
| | - Thierry Artzner
- Hôpitaux Universitaires de Strasbourg, 67000, Strasbourg, France
| | - Eleonora De Martin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Julia Wendon
- Liver Intensive Therapy Unit, Division of Inflammation Biology, King's College London, London, UK
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
- European Reference Network On Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
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Abstract
Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.
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Affiliation(s)
- Thomas N Smith
- Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
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9
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Crocombe D, Ahmed N, Balakrishnan I, Bordea E, Chau M, China L, Corless L, Danquah V, Dehbi HM, Dillon JF, Forrest EH, Freemantle N, Gear DP, Hollywood C, Hunter R, Jeyapalan T, Kallis Y, McPherson S, Munteanu I, Portal J, Richardson P, Ryder SD, Virk A, Wright G, O'Brien A. ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis-study protocol for an interventional randomised controlled trial. Trials 2022; 23:812. [PMID: 36167573 PMCID: PMC9513307 DOI: 10.1186/s13063-022-06727-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/08/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites. METHODS The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients' health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events. DISCUSSION This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis. TRIAL REGISTRATION ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central - Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).
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Affiliation(s)
- Dominic Crocombe
- UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
| | - Norin Ahmed
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Indran Balakrishnan
- Royal Free London NHS Foundation Trust, University College London, London, UK
| | - Ekaterina Bordea
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Marisa Chau
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Louise China
- UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
| | | | - Victoria Danquah
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Hakim-Moulay Dehbi
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK
| | - Ewan H Forrest
- Gastroenterology Unit, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Nick Freemantle
- University College London Comprehensive Clinical Trials Unit, London, UK
| | | | - Coral Hollywood
- Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
| | - Rachael Hunter
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Tasheeka Jeyapalan
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Yiannis Kallis
- The Blizard Institute, Queen Mary University of London, London, UK
| | - Stuart McPherson
- Liver Unit, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, The Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Iulia Munteanu
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Jim Portal
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Paul Richardson
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Stephen D Ryder
- NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Amandeep Virk
- University College London Comprehensive Clinical Trials Unit, London, UK
| | - Gavin Wright
- Mid & South Essex NHS Foundation Trust, Basildon, UK
| | - Alastair O'Brien
- UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK. a.o'.,University College London Comprehensive Clinical Trials Unit, London, UK. a.o'.,University College London Hospitals NHS Foundation Trust, London, UK. a.o'
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10
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White K, Tabah A, Ramanan M, Shekar K, Edwards F, Laupland KB. 90-day Case-Fatality in Critically ill Patients with Chronic Liver Disease Influenced by Presence of Portal Hypertension, Results from a Multicentre Retrospective Cohort Study. J Intensive Care Med 2022; 38:5-10. [PMID: 35892180 DOI: 10.1177/08850666221100408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Critical illness in patients with chronic liver disease (CLD) is increasing in occurrence, and by virtue of its adverse effect on prognosis, its presence may influence the decision to offer admission to intensive care units (ICU). Our objective was to examine the determinants and outcome of patients with CLD admitted to ICU. METHODS A retrospective cohort of patients admitted to four adult ICUs in Queensland, Australia from 2017 to 2019. Patients with mild or moderate-severe CLD were defined by the absence and presence of portal hypertension, respectively, and were was determined using granular ICU and state-wide administrative databases. The primary outcome was 90-day all cause case-fatality. RESULTS We included 3836 patients in the analysis, of which, 60 (2%) had mild liver disease and 132 (3%) had moderate-severe liver disease . Patients with CLD had higher incidence of other co-morbidities with the median adjusted-Charlson co-morbidity index (CCI) was 1 (interquartile range; IQR 0-3) for no CLD, 2 (IQR 1.5-4) for mild CLD, and 3 (IQR 2-5) for moderate-severe CLD. Case-fatality rates at 90 days was 17% for no CLD, 25% for mild CLD, and 41% for moderate-severe CLD. Among those with mild and moderate-severe CLD, an increased co-morbidity burden as measured by an adjusted CCI score of low (0-3), medium (4-5), high (6-7) and very high (>7) resulted in increasing case-fatality rates of 24-40%, 11-28.5%, 33-62%, and 50% respectively. Moderate-severe CLD, but not mild CLD, was independently associated with increased case-fatality at 90 days (Odds Ratio 1.58; 95% confidence interval 1.01-2.48; p = 0.004) after adjusting for medical co-morbidities and severity of illness using logistic regression analysis. CONCLUSIONS Although patients with moderate-severe CLD have an increased risk for 90-day case-fatality, patients with mild CLD are not at higher risk for death following ICU admission.
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Affiliation(s)
- Kyle White
- Intensive Care Unit, 1966Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Alexis Tabah
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Intensive Care Unit, 60077Redcliffe Hospital, Redcliffe, Queensland, Australia
| | - Mahesh Ramanan
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Intensive Care Unit, 60075Caboolture Hospital, Caboolture, Queensland, Australia
| | - Kiran Shekar
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Intensive Care Unit, The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Felicity Edwards
- 1969Queensland University of Technology (QUT), Brisbane, Queensland, Australia
| | - Kevin B Laupland
- 1969Queensland University of Technology (QUT), Brisbane, Queensland, Australia.,550021Department of Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
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Prognostic Role of MELD-Lactate in Cirrhotic Patients' Short- and Long-Term Prognosis, Stratified by Causes of Cirrhosis. Can J Gastroenterol Hepatol 2022; 2022:8449579. [PMID: 35392026 PMCID: PMC8983169 DOI: 10.1155/2022/8449579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 03/06/2022] [Accepted: 03/07/2022] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVES Recently, model for end-stage liver disease-lactate (MELD-LA) proved to be a superior predicting factor of inpatient mortality in patients with chronic liver disease. The study's objective was to evaluate the ability of MELD-LA to predict both short- and long-term mortality in critically ill cirrhotic patients stratified by causes of cirrhosis. MATERIALS AND METHODS This was a retrospective observational research of 469 cirrhotic patients entering intensive care unit. Clinical parameters and prognostic scores were measured and collected in the first 24 hours after entering intensive care unit. Follow-up duration was at least 5 years. Independent relationship between MELD-LA and mortality was evaluated by multivariate logistic regression analyses. Discrimination of scoring system was evaluated by the area under the receiver operating characteristic curve. Calibration of the score was evaluated by Hosmer-Lemeshow goodness of fit test for significance. RESULTS The MELD-LA score (odds ratio: 1.179, 95% confidence interval: 1.112-1.250, P < 0.001) was an independent risk factor for 15-day mortality. The area under the curve of MELD-LA was the highest (0.808, 95% confidence interval: 0.765-0.852) in predicting 15-day mortality and it had superior calibration. We found MELD-LA showed the best discrimination ability in cirrhotic patients caused by both alcohol and hepatitis (0.783, 95% confidence interval: 0.651-0.915) or alcohol alone (0.805, 95% confidence interval: 0.743-0.867). CONCLUSIONS MELD-LA performs better for predicting short-term prognosis in critically ill cirrhotic patients, especially caused by both alcohol and hepatitis or alcohol alone.
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Del Risco-Zevallos J, Andújar AM, Piñeiro G, Reverter E, Toapanta ND, Sanz M, Blasco M, Fernández J, Poch E. Management of acute renal replacement therapy in critically ill cirrhotic patients. Clin Kidney J 2022; 15:1060-1070. [PMID: 35664279 PMCID: PMC9155212 DOI: 10.1093/ckj/sfac025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Renal replacement therapy (RRT) in cirrhotic patients encompasses a number of issues related to the particular characteristics of this population, especially in the intensive care unit (ICU) setting. The short-term prognosis of cirrhotic patients with acute kidney injury is poor, with a mortality rate higher than 65% in patients with RRT requirement, raising questions about the futility of its initiation. Regarding the management of the RRT itself, there is still no consensus with respect to the modality (continuous versus intermittent) or the anticoagulation required to improve the circuit life, which is shorter than similar at-risk populations, despite the altered haemostasis in traditional coagulation tests frequently found in these patients. Furthermore, volume management is one of the most complex issues in this cohort, where tools used for ambulatory dialysis have not yet been successfully reproducible in the ICU setting. This review attempts to shed light on the management of acute RRT in the critically ill cirrhotic population based on the current evidence and the newly available tools. We will discuss the timing of RRT initiation and cessation, the modality, anticoagulation and fluid management, as well as the outcomes of the RRT in this population, and provide a brief review of the albumin extracorporeal dialysis from the point of view of a nephrologist.
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Affiliation(s)
| | | | - Gastón Piñeiro
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona. University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Enric Reverter
- Liver and Digestive ICU, Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Néstor David Toapanta
- Liver and Digestive ICU, Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Miquel Sanz
- Liver and Digestive ICU, Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Miquel Blasco
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona. University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Javier Fernández
- Liver and Digestive ICU, Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
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Maini AA, Becares N, China L, Tittanegro TH, Patel A, De Maeyer RPH, Zakeri N, Long TV, Ly L, Gilroy DW, O'Brien A. Monocyte dysfunction in decompensated cirrhosis is mediated by the prostaglandin E2-EP4 pathway. JHEP REPORTS : INNOVATION IN HEPATOLOGY 2021; 3:100332. [PMID: 34825153 PMCID: PMC8603213 DOI: 10.1016/j.jhepr.2021.100332] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 07/12/2021] [Accepted: 07/17/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Infection is a major problem in advanced liver disease secondary to monocyte dysfunction. Elevated prostaglandin (PG)E2 is a mediator of monocyte dysfunction in cirrhosis; thus, we examined PGE2 signalling in outpatients with ascites and in patients hospitalised with acute decompensation to identify potential therapeutic targets aimed at improving monocyte dysfunction. METHODS Using samples from 11 outpatients with ascites and 28 patients hospitalised with decompensated cirrhosis, we assayed plasma levels of PGE2 and lipopolysaccharide (LPS); performed quantitative real-time PCR on monocytes; and examined peripheral blood monocyte function. We performed western blotting and immunohistochemistry for PG biosynthetic machinery expression in liver tissue. Finally, we investigated the effect of PGE2 antagonists in whole blood using polychromatic flow cytometry and cytokine production. RESULTS We show that hepatic production of PGE2 via the cyclo-oxygenase 1-microsomal PGE synthase 1 pathway, and circulating monocytes contributes to increased plasma PGE2 in decompensated cirrhosis. Transjugular intrahepatic sampling did not reveal whether hepatic or monocytic production was larger. Blood monocyte numbers increased, whereas individual monocyte function decreased as patients progressed from outpatients with ascites to patients hospitalised with acute decompensation, as assessed by Human Leukocyte Antigen (HLA)-DR isotype expression and tumour necrosis factor alpha and IL6 production. PGE2 mediated this dysfunction via its EP4 receptor. CONCLUSIONS PGE2 mediates monocyte dysfunction in decompensated cirrhosis via its EP4 receptor and dysfunction was worse in hospitalised patients compared with outpatients with ascites. Our study identifies a potential drug target and therapeutic opportunity in these outpatients with ascites to reverse this process to prevent infection and hospital admission. LAY SUMMARY Patients with decompensated cirrhosis (jaundice, fluid build-up, confusion, and vomiting blood) have high infection rates that lead to high mortality rates. A white blood cell subset, monocytes, function poorly in these patients, which is a key factor underlying their sensitivity to infection. We show that monocyte dysfunction in decompensated cirrhosis is mediated by a lipid hormone in the blood, prostaglandin E2, which is present at elevated levels, via its EP4 pathway. This dysfunction worsens when patients are hospitalised with complications of cirrhosis compared with those in the outpatients setting, which supports the EP4 pathway as a potential therapeutic target for patients to prevent infection and hospitalisation.
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Key Words
- ACLF, acute-on-chronic liver failure
- AD, acute decompensation
- CAID, cirrhosis-associated immune dysfunction
- CM, classical monocytes
- COX, cyclooxygenase
- CRP, C-reactive protein
- Cyclo-oxygenase 1
- DSS, downstream synthases
- Decompensated cirrhosis
- EIA, enzyme immune assay
- FACS, polychromatic flow cytometric analysis
- HLA DR, human leukocyte antigen – DR isotype
- HLA-DR
- HPGD, 15-hydroxyprostaglandin dehydrogenase
- HVs, healthy volunteers
- IL6
- LC-MS/MS, liquid chromatography-tandem mass spectrometry
- LPS
- LPS, lipopolysaccharide
- MDMs, monocyte-derived macrophages
- MFI, mean fluorescence intensity
- Microsomal PGE synthase 1
- NASH, non-alcoholic steatohepatitis
- OPD, patients with refractory ascites attending hospital outpatient department for day case paracentesis
- PGE2, prostaglandin E2
- TIPS, transjugular intrahepatic portosystemic shunt insertion
- TNF
- TNFα, tumour necrosis factor alpha
- cPGES, cytosolic PGE synthase
- mPGES1, microsomal PGE synthase 1
- qPCR, quantitative PCR
- sCD14, soluble CD14
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Affiliation(s)
- Alexander A Maini
- Institute of Liver and Digestive Health, University College London, London, UK
| | - Natalia Becares
- Institute of Liver and Digestive Health, University College London, London, UK
| | - Louise China
- Institute of Liver and Digestive Health, University College London, London, UK
| | - Thais H Tittanegro
- Institute of Liver and Digestive Health, University College London, London, UK
| | - Amit Patel
- Division of Medicine, University College London, London, UK
| | | | - Nekisa Zakeri
- Institute of Liver and Digestive Health, University College London, London, UK
| | | | - Lucy Ly
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Derek W Gilroy
- Division of Medicine, University College London, London, UK
| | - Alastair O'Brien
- Institute of Liver and Digestive Health, University College London, London, UK
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Chandna S, Zarate ER, Gallegos-Orozco JF. Management of Decompensated Cirrhosis and Associated Syndromes. Surg Clin North Am 2021; 102:117-137. [PMID: 34800381 DOI: 10.1016/j.suc.2021.09.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications.
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Affiliation(s)
- Shaun Chandna
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Utah School of Medicine, 30 N 1900 E, SOM-4R118, Salt Lake City, UT 84106, USA
| | - Eduardo Rodríguez Zarate
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Utah School of Medicine, 30 N 1900 E, SOM-4R118, Salt Lake City, UT 84106, USA
| | - Juan F Gallegos-Orozco
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Utah School of Medicine, 30 N 1900 E, SOM-4R118, Salt Lake City, UT 84106, USA.
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15
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da Silveira F, Soares PHR, Marchesan LQ, da Fonseca RSA, Nedel WL. Assessing the prognosis of cirrhotic patients in the intensive care unit: What we know and what we need to know better. World J Hepatol 2021; 13:1341-1350. [PMID: 34786170 PMCID: PMC8568574 DOI: 10.4254/wjh.v13.i10.1341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/11/2021] [Accepted: 09/27/2021] [Indexed: 02/06/2023] Open
Abstract
Critically ill cirrhotic patients have high in-hospital mortality and utilize significant health care resources as a consequence of the need for multiorgan support. Despite this fact, their mortality has decreased in recent decades due to improved care of critically ill patients. Acute-on-chronic liver failure (ACLF), sepsis and elevated hepatic scores are associated with increased mortality in this population, especially among those not eligible for liver transplantation. No score is superior to another in the prognostic assessment of these patients, and both liver-specific and intensive care unit-specific scores have satisfactory predictive accuracy. The sequential assessment of the scores, especially the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure Consortium (CLIF)-SOFA scores, may be useful as an auxiliary tool in the decision-making process regarding the benefits of maintaining supportive therapies in this population. A CLIF-ACLF > 70 at admission or at day 3 was associated with a poor prognosis, as well as SOFA score > 19 at baseline or increasing SOFA score > 72. Additional studies addressing the prognostic assessment of these patients are necessary.
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Affiliation(s)
- Fernando da Silveira
- Programa de Pós-Graduação em Pneumologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 91430835, Brazil
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
| | - Pedro H R Soares
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
- Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 91430835, Brazil
| | - Luana Q Marchesan
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria 97105900, Brazil
| | | | - Wagner L Nedel
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
- Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre 91430835, Brazil.
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16
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EL-Ghannam M, Abdelrahman Y, Abu-Taleb H, Hassan M, Hassanien M, EL-Talkawy MD. Validation of Circom comorbidity score in critically-ill cirrhotic patients. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2021. [DOI: 10.1016/j.cegh.2021.100728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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17
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Lactate and Bilirubin Index: A New Indicator to Predict Critically Ill Cirrhotic Patients’ Prognosis. Can J Gastroenterol Hepatol 2021. [DOI: 10.1155/2021/6624177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objectives. We aimed to perform external validation of the prognostic value of the lactate and bilirubin (LB) index, a new indicator, and compare the ability of the LB index and other scoring systems to predict both short- and long-term mortality in critically ill cirrhotic patients. Materials and Methods. A number of 479 cirrhotic patients admitted into ICU were included in our research. We measured prognostic scores in the first 24 hours including LB index, Child–Pugh, SOFA, CLIF-SOFA, and MELD scores. The LB index was calculated as follows: ln [1000 × lactate (mmol/L) × bilirubin (µmol/L)]/2. The primary outcomes were 28-day and 3-year all-cause mortality. Multivariate logistic regression analyses were used to investigate the independent association between the LB index and the mortality in critically ill cirrhotic patients. The area under the receiver operating characteristic curve was used to assess the prediction accuracy of short- and long-term mortality of the clinical score. Calibration of the score was evaluated by Hosmer–Lemeshow goodness-of-fit test for significance. Results. Multivariate logistic regression analysis identified that the LB index (odds ratio: 5.487, 95% confidence interval: 3.542–8.501,
) was the strongest predictor for 28-day mortality. The LB index gave the highest area under the curve (0.791, 95% confidence interval: 0.747–0.836) in predicting 28-day mortality. For predicting 3-year mortality, the model for end-stage liver disease (MELD) score showed better discrimination ability with an area under the curve of 0.726 (95% confidence interval: 0.680–0.771). The risk of mortality significantly increased when the clinical scores were ≥ the optimal cutoff values. Conclusions. The LB index, a simple prognostic indicator, performs well in predicting critically ill cirrhotic patients’ short-term prognosis, while, for long-term prognosis, the MELD score is more appropriate.
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18
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Trusson R, Brunot V, Larcher R, Platon L, Besnard N, Moranne O, Barbar S, Serre JE, Klouche K. Short- and Long-Term Outcome of Chronic Dialyzed Patients Admitted to the ICU and Assessment of Prognosis Factors: Results of a 6-Year Cohort Study. Crit Care Med 2020; 48:e666-e674. [PMID: 32697507 DOI: 10.1097/ccm.0000000000004412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Data about end-stage kidney disease patients admitted to the ICU are scarce, dated, and mostly limited to short-term survival. The aim of this study was to assess the short- and long-term outcome and to determine the prognostic factors for end-stage kidney disease patients admitted to the ICU. DESIGN Prospective observational study. SETTING Medical ICUs in two university hospitals. PATIENTS Consecutive end-stage kidney disease patients admitted in two ICUs between 2012 and 2017. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Renal replacement therapy variables, demographic, clinical, and biological data were collected. The requirement of mechanical ventilation and vasopressive drugs were also collected. In-ICU and one-year mortality were estimated and all data were analyzed in order to identify predictive factors of short and long-term mortality. A total of 140 patients were included, representing 1.7% of total admissions over the study period. Septic shock was the main reason for admission mostly of pulmonary origin. Median Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score were at 63 and 6.7, respectively. In-ICU, hospital, and 1-year mortality were 41.4%, 46.4%, and 63%, respectively. ICU mortality was significantly higher as compared with ICU control group non-end-stage kidney disease (25% vs 41.4%; p = 0.005). By multivariate analysis, the short-term outcome was significantly associated with nonrenal Sequential Organ Failure Assessment score, and with the requirement of mechanical ventilation or/and vasoconstrictive agents during ICU stay. One-year mortality was associated with increased dialysis duration (> 3 yr) and phosphatemia (> 2.5 mmol/L), with lower albuminemia (< 30 g/L) and nonrenal Sequential Organ Failure Assessment greater than 8. CONCLUSIONS End-stage kidney disease patients presented frequently severe complications requiring critical care that induced significant short- and long-term mortality. ICU and hospital mortality depended mainly on the severity of the critical event reflected by Sequential Organ Failure Assessment score and the need of mechanical ventilation and/or catecholamines. One-year mortality was associated with both albuminemia and phosphatemia and with prior duration of chronic dialysis treatment, and with organ failure at ICU admission.
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Affiliation(s)
- Rémi Trusson
- Department of Intensive Care Medicine, University Hospital, Nimes, France
| | - Vincent Brunot
- Department of Intensive Care Medicine, Lapeyronie University Hospital, Montpellier, France
| | - Romaric Larcher
- Department of Intensive Care Medicine, Lapeyronie University Hospital, Montpellier, France
- PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France
| | - Laura Platon
- Department of Intensive Care Medicine, Lapeyronie University Hospital, Montpellier, France
| | - Noémie Besnard
- Department of Intensive Care Medicine, Lapeyronie University Hospital, Montpellier, France
| | - Olivier Moranne
- Nephrology-Dialysis-Apheresis Unit, University Hospital, Nimes, France
- UPRES EA2415, Laboratory of Biostatistics, Epidemiology, Clinical Research and Health Economics, University of Montpellier, Montpellier, France
| | - Saber Barbar
- Department of Intensive Care Medicine, University Hospital, Nimes, France
| | - Jean-Emmanuel Serre
- Department of Nephrology, Lapeyronie University Hospital, Montpellier, France
| | - Kada Klouche
- Department of Intensive Care Medicine, Lapeyronie University Hospital, Montpellier, France
- PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France
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19
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Lindenmeyer CC, Flocco G, Sanghi V, Lopez R, Kim AJ, Niyazi F, Mehta NA, Kapoor A, Carey WD, Mireles-Cabodevila E, Romero-Marrero C. LIV-4: A novel model for predicting transplant-free survival in critically ill cirrhotics. World J Hepatol 2020; 12:298-311. [PMID: 32742572 PMCID: PMC7364328 DOI: 10.4254/wjh.v12.i6.298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 05/15/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Critically ill patients with cirrhosis, particularly those with acute decompensation, have higher mortality rates in the intensive care unit (ICU) than patients without chronic liver disease. Prognostication of short-term mortality is important in order to identify patients at highest risk of death. None of the currently available prognostic models have been widely accepted for use in cirrhotic patients in the ICU, perhaps due to complexity of calculation, or lack of universal variables readily available for these patients. We believe a survival model meeting these requirements can be developed, to guide therapeutic decision-making and contribute to cost-effective healthcare resource utilization.
AIM To identify markers that best identify likelihood of survival and to determine the performance of existing survival models.
METHODS Consecutive cirrhotic patients admitted to a United States quaternary care center ICU between 2008-2014 were included and comprised the training cohort. Demographic data and clinical laboratory test collected on admission to ICU were analyzed. Area under the curve receiver operator characteristics (AUROC) analysis was performed to assess the value of various scores in predicting in-hospital mortality. A new predictive model, the LIV-4 score, was developed using logistic regression analysis and validated in a cohort of patients admitted to the same institution between 2015-2017.
RESULTS Of 436 patients, 119 (27.3%) died in the hospital. In multivariate analysis, a combination of the natural logarithm of the bilirubin, prothrombin time, white blood cell count, and mean arterial pressure was found to most accurately predict in-hospital mortality. Derived from the regression coefficients of the independent variables, a novel model to predict inpatient mortality was developed (the LIV-4 score) and performed with an AUROC of 0.86, compared to the Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment, and Royal Free Hospital Score, which performed with AUROCs of 0.81, 0.80, and 0.77, respectively. Patients in the internal validation cohort were substantially sicker, as evidenced by higher Model for End-Stage Liver Disease, Model for End-Stage Liver Disease-Sodium, Acute Physiology and Chronic Health Evaluation III, SOFA and LIV-4 scores. Despite these differences, the LIV-4 score remained significantly higher in subjects who expired during the hospital stay and exhibited good prognostic values in the validation cohort with an AUROC of 0.80.
CONCLUSION LIV-4, a validated model for predicting mortality in cirrhotic patients on admission to the ICU, performs better than alternative liver and ICU-specific survival scores.
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Affiliation(s)
- Christina C Lindenmeyer
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Gianina Flocco
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Vedha Sanghi
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Rocio Lopez
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44106, United States
| | - Ahyoung J Kim
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Fadi Niyazi
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Neal A Mehta
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Aanchal Kapoor
- Department of Critical Care Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - William D Carey
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
| | | | - Carlos Romero-Marrero
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
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Management of liver failure in general intensive care unit. Anaesth Crit Care Pain Med 2020; 39:143-161. [PMID: 31525507 DOI: 10.1016/j.accpm.2019.06.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 06/30/2019] [Indexed: 12/11/2022]
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21
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Neonatal Sepsis Alters the Excitability of Regular Spiking Cells in the Nucleus of the Solitary Tract in Rats. Shock 2019; 54:265-271. [DOI: 10.1097/shk.0000000000001453] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Baudry T, Hernu R, Valleix B, Jahandiez V, Faucher E, Simon M, Cour M, Argaud L. Cirrhotic Patients Admitted to the ICU With Septic Shock: Factors Predicting Short and Long-Term Outcome. Shock 2019; 52:408-413. [PMID: 30395082 DOI: 10.1097/shk.0000000000001282] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Cirrhotic patients with septic shock have a poor prognosis in ICU compared to general population of critically ill patients. Little is known about long-term outcome in these patients. We performed a retrospective analysis of a prospective cohort of cirrhotic patients with septic shock. The aim of this study was to describe both short and long-term outcomes and to evaluate factors predicting mortality. Data from 149 patients were analyzed (mean age: 60 ± 11 years, sex ratio: 2.4). Mortality rate in the ICU was 54% and at 1 year it was 73%. Among factors associated with adverse outcome, independent factors predicting ICU mortality were early need for renal replacement therapy (odds ratios, OR 13.95, 95% confidence interval, CI 3.30; 59.03) and arterial lactate >5 mmol.L (OR 7.27, 95% CI 2.92; 18.10), and early use of mechanical ventilation (OR 3.05, 95% CI 1.08; 8.58). For 1-year mortality, independent prognostic factors were the need for renal replacement therapy during ICU stay (OR 9.60, 95% CI 2.90; 31.82), prothrombin time ≤40% (OR 3.47, 95% CI 1.43; 8.43), and Charlson score (OR 1.36 per point, 95% CI 1.11; 1.67). The results emphasize the poor prognosis of cirrhotic patients with septic shock admitted to the ICU. The need for organ supports appears to be a better predictor of short-term outcome than the underlying hepatic disease. Renal replacement therapy is associated with both short and long-term outcomes.
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Affiliation(s)
- Thomas Baudry
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Romain Hernu
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Baptiste Valleix
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Vincent Jahandiez
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Etienne Faucher
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Marie Simon
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Martin Cour
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
- Faculté de Médecine Lyon-Est, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France
| | - Laurent Argaud
- Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
- Faculté de Médecine Lyon-Est, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France
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Dynamic Prognostication in Critically Ill Cirrhotic Patients With Multiorgan Failure in ICUs in Europe and North America: A Multicenter Analysis. Crit Care Med 2019; 46:1783-1791. [PMID: 30106759 DOI: 10.1097/ccm.0000000000003369] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To evaluate the Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score in acute on chronic liver failure patients admitted to ICUs from different global regions and compare discrimination ability with previously published scores. DESIGN Retrospective pooled analysis. SETTING Academic ICUs in Canada (Edmonton, Vancouver) and Europe (Paris, Barcelona, Chronic liver failure/Acute-on-Chronic Liver Failure in Cirrhosis [CANONIC] study). PATIENTS Sample of analysis of 867 cirrhotic patients with acute on chronic liver failure admitted to ICU. Cumulative incidence functions of death were estimated by acute on chronic liver failure grade at admission and at day 3. Survival discrimination abilities of Chronic Liver Failure-Consortium Acute on Chronic Liver Failure, Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Child-Turcotte-Pugh scores were compared. INTERVENTIONS ICU admission for organ support. MEASUREMENTS AND MAIN RESULTS At admission 169 subjects (19%) had acute on chronic liver failure 1, 302 (35%) acute on chronic liver failure 2, and 396 (46%) had acute on chronic liver failure 3 with 90-mortality rates of 33%, 40%, and 74%, respectively (p < 0.001). At admission, Chronic Liver Failure-Consortium Acute on Chronic Liver Failure demonstrated superior discrimination at 90 days compared with Acute Physiology and Chronic Health Evaluation II (n = 532; concordance index 0.67 vs 0.62; p = 0.0027) and Child-Turcotte-Pugh (n = 666; 0.68 vs 0.64; p = 0.0035), but not Model for End-Stage Liver Disease (n = 845; 0.68 vs 0.67; p = 0.3). A Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score greater than 70 at admission or on day 3 was associated with 90-day mortality rates of approximately 90%. Ninety-day mortality in grade 3 acute on chronic liver failure patients at admission who demonstrated improvement by day 3 was 40% (vs 79% in patients who did not). CONCLUSIONS The Chronic Liver Failure-Consortium Acute on Chronic Liver Failure demonstrated better discrimination at day 28 and day 90 compared with Acute Physiology and Chronic Health Evaluation II and Child-Turcotte-Pugh. Patients who demonstrated clinical improvement post-ICU admission (e.g., acute on chronic liver failure 3 to 1 or 2) at day 3 had better outcomes than those who did not. In high-risk ICU patients (Chronic Liver Failure-Consortium Acute on Chronic Liver Failure > 70), decisions regarding transition to palliation should be explored between patient families and the ICU providers after a short trial of therapy.
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Bauer M, Fuhrmann V, Wendon J. Pulmonary complications in liver disease. Intensive Care Med 2019; 45:1433-1435. [PMID: 31375864 PMCID: PMC6773671 DOI: 10.1007/s00134-019-05721-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 07/28/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Michael Bauer
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.
| | - Valentin Fuhrmann
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.,Department of Medicine B, University Hospital Münster, Münster, Germany
| | - Julia Wendon
- Department of Critical Care, Kings College Hospital Foundation Trust, London, UK
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Prognostic value of international normalized ratio to albumin ratio among critically ill patients with cirrhosis. Eur J Gastroenterol Hepatol 2019; 31:824-831. [PMID: 30601338 DOI: 10.1097/meg.0000000000001339] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Critically ill patients with cirrhosis are at an increased risk of mortality. Our study aimed to externally validate the ability of the prothrombin time-international normalized ratio to albumin ratio (PTAR), an objective and simple scoring system, to predict 90-day mortality in critically ill patients with cirrhosis. PATIENTS AND METHODS A total of 865 patients were entered into the study, and all the participants were followed up for at least 90 days. Clinical parameters on the first day of intensive care unit admission were included to compare survivors with nonsurvivors. RESULTS After multivariable adjustment, the association between the risk of 90-day mortality and PTAR remained statistically significant with a hazard ratio of 2.71 (95% confidence interval: 1.99-3.68). The PTAR score showed good discrimination ability for predicting 90-day mortality with an area under receiver operating characteristic curve of 0.72 (95% confidence interval: 0.68-0.75). To improve its feasibility, we regrouped the PTAR scores into three levels of risk (low risk: <0.55, intermediate risk: 0.55-1.00, and high risk: ≥1.00); the 90-day mortality rates were 20.1% (74/368), 41.7% (168/403), and 73.4% (69/94), respectively. CONCLUSION The PTAR score system is a convenient and practical tool for predicting the prognosis of critically ill patients with cirrhosis.
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Satti R, Abid NUH, Bottaro M, De Rui M, Garrido M, Raoufy MR, Montagnese S, Mani AR. The Application of the Extended Poincaré Plot in the Analysis of Physiological Variabilities. Front Physiol 2019; 10:116. [PMID: 30837892 PMCID: PMC6390508 DOI: 10.3389/fphys.2019.00116] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 01/30/2019] [Indexed: 01/12/2023] Open
Abstract
The Poincaré plot is a geometrical technique used to visualize and quantify the correlation between two consecutive data points in a time-series. Since the dynamics of fluctuations in physiological rhythms exhibit long-term correlation and memory, this study aimed to extend the Poincaré plot by calculating the correlation between sequential data points in a time-series, rather than between two consecutive points. By incorporating this so-called lag, we hope to integrate a temporal aspect into quantifying the correlation, to depict whether a physiological system holds prolonged association between events separated by time. In doing so, it attempts to instantaneously characterize the intrinsic behavior of a complex system. We tested this hypothesis on three different physiological time-series: heart rate variability in patients with liver cirrhosis, respiratory rhythm in asthma and body temperature fluctuation in patients with cirrhosis, to evaluate the potential application of the extended Poincaré method in clinical practice. When studying the cardiac inter-beat intervals, the extended Poincaré plot revealed a stronger autocorrelation for patients with decompensated liver cirrhosis compared to less severe cases using Pearson's correlation coefficient. In addition, long-term variability (known as SD2 in the extended Poincaré plot) appeared as an independent prognostic variable. This holds significance by acting as a non-invasive tool to evaluate patients with chronic liver disease and potentially facilitate transplant selection as an adjuvant to traditional criteria. For asthmatics, employing the extended Poincaré plot allowed for a non-invasive tool to differentially diagnose various classifications of respiratory disease. In the respiratory inter-breath interval analysis, the receiver operating characteristic (ROC) curve provided evidence that the extension of the Poincaré plot holds a greater advantage in the classification of asthmatic patients, over the traditional Poincaré plot. Lastly, the analysis of body temperature from patients using the extended Poincaré plot helped identify inpatients from outpatients with cirrhosis. Through these analyses, the extended Poincaré plot provided unique and additional information which could potentially make a difference in clinical practice. Conclusively, the potential use of our work lies in its possible application of predicting mortality for the organ allocation procedure in patients with cirrhosis and non-invasively distinguish between atopic and non-atopic asthma.
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Affiliation(s)
- Reem Satti
- UCL Division of Medicine, University College London, London, United Kingdom
| | - Noor-Ul-Hoda Abid
- UCL Division of Medicine, University College London, London, United Kingdom
| | - Matteo Bottaro
- Department of Medicine, University of Padova, Padova, Italy
| | - Michele De Rui
- Department of Medicine, University of Padova, Padova, Italy
| | - Maria Garrido
- Department of Medicine, University of Padova, Padova, Italy
| | | | | | - Ali R. Mani
- UCL Division of Medicine, University College London, London, United Kingdom
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Nataj A, Eftekhari G, Raoufy MR, Mani AR. The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure. Physiol Meas 2018; 39:114008. [PMID: 30475741 DOI: 10.1088/1361-6579/aaea10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The network of interactions between different organs is impaired in liver cirrhosis. Liver cirrhosis is associated with multi-system involvement, which eventually leads to multiple organ failure. This process is accelerated by a precipitating factor such as bacterial infection, which leads to respiratory distress, circulatory shock, neural dysfunction and very high mortality. Cirrhotic patients often have blunted respiratory sinus arrhythmia and impaired cardio-respiratory variability. Fractal-like mechanical ventilation is reported to enhance respiratory sinus arrhythmia and attenuate respiratory distress in experimental models. In the present study we hypothesise that fractal-like mechanical ventilation may improve the outcome of cirrhotic rats with multiple organ failure. APPROACH Cirrhosis was induced by chronic biliary obstruction in rats. Acute multiple organ failure was induced by intraperitoneal injection of bacterial endotoxin in cirrhotic rats. The effect of conventional mechanical ventilation (with constant tidal volume and respiratory rate) or fractal-like ventilation (with the same average but variable tidal volume and respiratory rate) were assessed on vital signs, oxygen saturation and plasma alanine aminotransferase in anaesthetised cirrhotic rats. MAIN RESULTS We demonstrated that fractal-like mechanical ventilation was accompanied by improved oxygen saturation, reduced heart rate and decreased liver injury following injection of bacterial endotoxin. Moreover, variable mechanical ventilation in cirrhotic rats reduced mortality and prevented a fall in short-term heart rate variability following endotoxin challenge in comparison with rats with constant mechanical ventilation. SIGNIFICANCE We suggest further investigations into the beneficial effects of fractal-like ventilation strategy in critically ill patients with liver failure requiring organ support and mechanical ventilation.
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Affiliation(s)
- Arman Nataj
- Faculty of Medical Sciences, Department of Physiology, Tarbiat Modares University, Tehran, Iran. These authors are joint first authors
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Khaldi M, Lemaitre E, Louvet A, Artru F. Insuffisance rénale aiguë et syndrome hépatorénal chez le patient cirrhotique : actualités diagnostiques et thérapeutiques. MEDECINE INTENSIVE REANIMATION 2018. [DOI: 10.3166/rea-2018-0076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
La survenue d’une insuffisance rénale aiguë ou AKI (acute kidney injury) chez un patient cirrhotique est un événement de mauvais pronostic. Parmi les AKI, une entité spécifique au patient cirrhotique décompensé est le syndrome hépatorénal (SHR) dont la définition ainsi que la stratégie thérapeutique ont été réactualisées récemment. La prise en charge de l’AKI hors SHR n’est pas spécifique au patient cirrhotique. La prise en charge du SHR repose sur l’association d’un traitement vasoconstricteur intraveineux et d’un remplissage vasculaire par sérum d’albumine concentrée. Cette association thérapeutique permet d’améliorer le pronostic des patients répondeurs. En contexte d’AKI chez le patient cirrhotique, l’épuration extrarénale (EER) peut être envisagée en cas de non-réponse au traitement médical. La décision de débuter une prise en charge invasive avec EER dépend principalement de la présence d’un projet de transplantation hépatique (TH). En l’absence d’un tel projet, cette décision devrait être prise après évaluation du pronostic à court terme du patient dépendant du nombre de défaillance d’organes et d’autres variables telles que l’âge ou les comorbidités. L’objectif de cette mise au point est de discuter des récentes modifications de la définition de l’AKI et en particulier du SHR chez les patients cirrhotiques, de détailler la prise en charge spécifique du SHR et d’évoquer les processus décisionnels menant ou non à l’instauration d’une EER chez les patients non répondeurs au traitement médical en milieu réanimatoire.
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China L, Skene SS, Bennett K, Shabir Z, Hamilton R, Bevan S, Chandler T, Maini AA, Becares N, Gilroy D, Forrest EH, O’Brien A. ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for an interventional randomised controlled trial. BMJ Open 2018; 8:e023754. [PMID: 30344180 PMCID: PMC6196858 DOI: 10.1136/bmjopen-2018-023754] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds to and inactivates this immune-suppressive lipid mediator. Human albumin solution (HAS) could thus be repurposed as an immune-restorative drug in these patients.This is a phase III randomised controlled trial (RCT) to verify whether targeting a serum albumin level of ≥35 g/L in hospitalised patients with decompensated cirrhosis using repeated intravenous infusions of 20% HAS will reduce incidence of infection, renal dysfunction and mortality for the treatment period (maximum 14 days or discharge if <14 days) compared with standard medical care. METHODS AND ANALYSIS Albumin To prevenT Infection in chronic liveR failurE stage 2 is a multicentre, open-label, interventional RCT. Patients with decompensated cirrhosis admitted to the hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Patients randomised to intravenous HAS will have this administered, according to serum albumin levels, for up to 14 days or discharge. The infusion protocol aims to increase serum albumin to near-normal levels.The composite primary endpoint is: new infection, renal dysfunction or mortality within the trial treatment period. Secondary endpoints include mortality at up to 6 months, incidence of other organ failures, cost-effectiveness and quality of life outcomes and time to liver transplant. The trial will recruit 866 patients at more than 30 sites across the UK. ETHICSANDDISSEMINATION Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the National Institute for Health Research (ISRCTN 14174793). This manuscript refers to version 6.0 of the protocol. Results will be disseminated through peer-reviewed journals and international conferences. Recruitment of the first participant occurred on 25 January 2016.
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Affiliation(s)
- Louise China
- Division of Medicine, University College London, London, UK
| | - Simon S Skene
- School of Biosciences and Medicine, University of Surrey, Guildford, UK
| | - Kate Bennett
- Comprehensive Clinical Trials Unit, UCL, London, UK
| | | | | | - Scott Bevan
- Comprehensive Clinical Trials Unit, UCL, London, UK
| | | | | | | | - Derek Gilroy
- Division of Medicine, University College London, London, UK
| | - Ewan H Forrest
- Department of Gastroenterology, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
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China L, Skene SS, Shabir Z, Maini A, Sylvestre Y, Bennett K, Bevan S, O'Beirne J, Forrest E, Portal J, Ryder S, Wright G, Gilroy DW, O'Brien A. Administration of Albumin Solution Increases Serum Levels of Albumin in Patients With Chronic Liver Failure in a Single-Arm Feasibility Trial. Clin Gastroenterol Hepatol 2018; 16:748-755.e6. [PMID: 28911947 PMCID: PMC6168936 DOI: 10.1016/j.cgh.2017.09.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 08/21/2017] [Accepted: 09/06/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Infections are life-threatening to patients with acute decompensation and acute-on-chronic liver failure (AD/ACLF). Patients with AD/ACLF have prostaglandin E2-mediated immune suppression, which can be reversed by administration of albumin; infusion of 20% human albumin solution (HAS) might improve outcomes of infections. We performed a feasibility study to determine optimal trial design, assess safety, and validate laboratory assessments of immune function to inform design of a phase 3 trial. METHODS We performed a prospective multicenter, single-arm, open-label trial of 79 patients with AD/ACLF and levels of albumin lower than 30 g/L, seen at 10 hospitals in the United Kingdom from May through December 2015. Patients were given daily infusions of 20% HAS, based on serum levels, for 14 days or until discharge from the hospital. Rates of infection, organ dysfunction, and in-hospital mortality were recorded. The primary end point was daily serum albumin level during the treatment period. Success would be demonstrated if 60% achieved and maintained serum albumin levels at or above 30 g/L on at least one third of days with recorded levels. RESULTS The patients' mean model for end-stage disease score was 20.9 ± 6.6. The primary end point (albumin ≥30 g/L on at least one third of days recorded) was achieved by 68 of the 79 patients; 75% of administrations were in accordance with suggested dosing regimen. Mean treatment duration was 10.3 days (104 ± 678 mL administered). There were 8 deaths and 13 serious adverse events, considered by the independent data-monitoring committee to be consistent with those expected. Twelve of 13 patients that developed either respiratory or cardiovascular dysfunction (based on ward-based clinical definitions) as their only organ dysfunction were alive at 30 days compared with 1 of 3 that developed renal dysfunction. Only 1 case of brain dysfunction was recorded. CONCLUSIONS In a feasibility trial, we found that administration of HAS increased serum levels of albumin in patients with AD/ACLF. The dosing regimen was acceptable at multiple sites and deemed safe by an independent data-monitoring committee. We also developed a robust system to record infections. The poor prognosis for patients with renal dysfunction was confirmed. However, patients with cardiovascular or respiratory dysfunction had good outcomes, which is counterintuitive. Severe encephalopathy appeared substantially under-reported, indicating that ward-based assessment of these parameters cannot be recorded with sufficient accuracy for use as a primary outcome in phase 3 trials. Trial registration no: EudraCT 2014-002300-24 and ISRCTN14174793.
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Affiliation(s)
- Louise China
- Division of Medicine, University College London, United Kingdom.
| | - Simon S Skene
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
| | - Zainib Shabir
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
| | - Alexander Maini
- Division of Medicine, University College London, United Kingdom
| | - Yvonne Sylvestre
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
| | - Kate Bennett
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
| | - Scott Bevan
- Comprehensive Clinical Trials Unit, University College London, United Kingdom
| | - James O'Beirne
- Royal Free National Health Service Trust, London, United Kingdom
| | - Ewan Forrest
- Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Jim Portal
- Bristol Royal Infirmary, Bristol, United Kingdom
| | - Steve Ryder
- Nottingham University Hospital, Nottingham, United Kingdom
| | - Gavin Wright
- Basildon University Hospital, Essex, United Kingdom
| | - Derek W Gilroy
- Division of Medicine, University College London, United Kingdom
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McPhail MJW, Parrott F, Wendon JA, Harrison DA, Rowan KA, Bernal W. Incidence and Outcomes for Patients With Cirrhosis Admitted to the United Kingdom Critical Care Units. Crit Care Med 2018; 46:705-712. [PMID: 29309369 PMCID: PMC5899891 DOI: 10.1097/ccm.0000000000002961] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. DESIGN Retrospective cohort study. SETTING Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. PATIENTS Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and Chronic Health Evaluation II score for patients with alcohol-related liver disease in 2012 was 20.6 (7.0) and 19.0 (7.2) for non-alcohol-related liver disease (p < 0.001). In adjusted analysis, alcohol-related liver disease was associated with increased risk of death (odds ratio, 1.51 [95% CI, 1.42-1.62; p < 0.001]) with a year-on-year reduction in hospital mortality (adjusted odds ratio, 0.95/yr, [0.94-0.96, p < 0.001]). CONCLUSIONS More patients with cirrhosis are being admitted to critical care units but with increasing survival rates. Patients with alcohol-related liver disease have reduced survival rates partly explained by higher levels of organ failure at admission. Patients with cirrhosis and organ failure warrant a trial of organ support and universal prognostic pessimism is not justified.
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Affiliation(s)
- Mark JW McPhail
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, Denmark Hill, London
| | | | - Julia A Wendon
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, Denmark Hill, London
| | | | - Kathy A Rowan
- Intensive Care National Audit & Research Centre, London
| | - William Bernal
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, Denmark Hill, London
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Skurzak S, Carrara G, Rossi C, Nattino G, Crespi D, Giardino M, Bertolini G. Cirrhotic patients admitted to the ICU for medical reasons: Analysis of 5506 patients admitted to 286 ICUs in 8years. J Crit Care 2018; 45:220-228. [PMID: 29604566 DOI: 10.1016/j.jcrc.2018.03.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 02/22/2018] [Accepted: 03/16/2018] [Indexed: 12/29/2022]
Abstract
PURPOSE To describe characteristics and prognostic factors of cirrhotic patients admitted to a representative sample of Italian intensive care units (ICUs). MATERIALS AND METHODS All patients admitted to 286 ICUs for medical reasons between 2002 and 2010 (excluding 2007) were considered. A logistic regression model was developed on cirrhotics to predict hospital mortality. The prediction was applied to different subgroups defined by both the level of unit expertise with cirrhotics and the overall unit performance, and compared to the actual mortality. RESULTS 5506 cirrhotic patients (32.1% admitted to the ICU for non-cirrhotic-related reasons) were compared to 130,477 controls. Hospital mortality was higher in cirrhotics (57.2% vs. 35.0%, p<0.001). ICU volume of cirrhotic patients did not influence mortality, while the overall performance of the unit did. The standardized mortality ratio for overall lower-performing units was 1.09 (95%CI: 1.05-1.14), for the average-performing units it was 1.01 (95%CI: 0.98-1.04), for the higher-performing units it was 0.92 (95%CI: 0.89-0.96). CONCLUSIONS The outcome of critically ill cirrhotic patients is quite poor, but not to limit their admission to the ICU. When cirrhosis accompanies other acute conditions, the general level of intensive care medicine is more important than the specific liver-oriented expertise in treating these patients.
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Affiliation(s)
- Stefano Skurzak
- Servizio di Anestesia e Rianimazione 2 Città della Salute e della Scienza di Torino, Italy
| | - Greta Carrara
- GiViTI Coordinating Center, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy.
| | - Carlotta Rossi
- GiViTI Coordinating Center, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy
| | - Giovanni Nattino
- GiViTI Coordinating Center, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy
| | - Daniele Crespi
- GiViTI Coordinating Center, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy
| | - Michele Giardino
- GiViTI Coordinating Center, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy
| | - Guido Bertolini
- GiViTI Coordinating Center, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy
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Fuhrmann V, Whitehouse T, Wendon J. The ten tips to manage critically ill patients with acute-on-chronic liver failure. Intensive Care Med 2018; 44:1932-1935. [DOI: 10.1007/s00134-018-5078-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 01/24/2018] [Indexed: 12/25/2022]
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Majumdar A, Bailey M, Kemp WM, Bellomo R, Roberts SK, Pilcher D. Declining mortality in critically ill patients with cirrhosis in Australia and New Zealand between 2000 and 2015. J Hepatol 2017; 67:1185-1193. [PMID: 28802877 DOI: 10.1016/j.jhep.2017.07.024] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 07/07/2017] [Accepted: 07/24/2017] [Indexed: 02/09/2023]
Abstract
BACKGROUND & AIMS Few studies have described the outcomes of patients with cirrhosis receiving intensive care unit (ICU) admission at a population level. We aimed to describe trends in the mortality of such patients in Australia and New Zealand (ANZ), and to investigate the relationship with associated organ failures. METHODS We studied patients admitted to 172 ICUs on a non-elective basis, with and without cirrhosis between January 1st 2000 and December 31st 2015, as recorded by the ANZ Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. We assessed severity of illness on admission using organ failure models and acute physiology scores. The primary outcome was hospital mortality. RESULTS Patients with cirrhosis accounted for 17,044 of 776,873 non-elective ICU admissions (2.2%). Cirrhosis hospital mortality was 32.4% compared to 16.9% in the non-cirrhotic group (p<0.0001). After adjustment for key confounders, cirrhosis had an independent effect on mortality with an odds ratio (OR) of 1.10 (1.06-1.15). There was no difference in the adjusted annual decline in mortality between patients with or without cirrhosis (OR 0.96 [0.95-0.97] vs. 0.96 [0.96-0.96], p=0.67). No difference was seen in the adjusted decline in mortality of patients with cirrhosis when stratified by mechanical ventilation (p=0.92), liver transplant centre status (p=0.27) or presence of sepsis (p=0.09). Mortality increased with number of organ failures, however, the presence of cirrhosis was not found to affect this relationship (p=0.33). CONCLUSIONS The mortality of patients with cirrhosis admitted to ICU on a non-elective basis has declined significantly over time, comparable to patients without cirrhosis, and is predominantly governed by the number of organ failures. Outcomes are similar between non-liver transplant ICUs and liver transplant centres. LAY SUMMARY The outcomes of patients with liver cirrhosis admitted to intensive care units (ICUs) have been previously regarded as poor. We have demonstrated that in Australia and New Zealand, annual in-hospital death rates following ICU admission in this patient group are lower than previously reported, have improved over 16years to 29% and are at a rate similar to patients without cirrhosis. Our data justify recommendations that advocate better access to intensive care for patients with cirrhosis.
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Affiliation(s)
- Avik Majumdar
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia; AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
| | - Michael Bailey
- Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Australia; ANZICS Centre for Outcome and Resource Evaluation (CORE), Melbourne, Australia
| | - William M Kemp
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - Rinaldo Bellomo
- Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, The Alfred Hospital, Melbourne, Australia
| | - David Pilcher
- Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Australia; ANZICS Centre for Outcome and Resource Evaluation (CORE), Melbourne, Australia; Department of Intensive Care, The Alfred Hospital, Melbourne, Australia
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Warren A, Soulsby CR, Puxty A, Campbell J, Shaw M, Quasim T, Kinsella J, McPeake J. Long-term outcome of patients with liver cirrhosis admitted to a general intensive care unit. Ann Intensive Care 2017; 7:37. [PMID: 28374334 PMCID: PMC5378565 DOI: 10.1186/s13613-017-0257-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 03/08/2017] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES The prevalence of liver cirrhosis is increasing, and many patients have acute conditions requiring consideration of intensive care. This study aims to: (a) report the outcome at 12 months of patients with cirrhosis admitted to ICU, (b) identify factors predictive of long-term mortality and (c) evaluate the ability of scoring systems to predict long-term outcome. DESIGN Observational cohort study. SETTING General adult critical care unit in a UK teaching hospital. PATIENTS Eighty-four patients admitted to critical care between June 2012 and December 2013. PRIMARY OUTCOME MEASURES Cumulative survival at ICU discharge, hospital discharge and 12 months. RESULTS Eighty-four patients with diagnosed cirrhosis were followed up at 12 months. Clinical variables collected at ICU admission were entered into a multivariate regression analysis for mortality and eight predetermined scoring systems calculated. Cumulative survival at ICU discharge, hospital discharge and 12 months was 64.8, 47.1 and 44.1%, respectively. Twelve months of cumulative survival in patients with Child-Pugh class A was 100%, class B was 50% and class C was 25% (log rank p = 0.002). Independent predictors of mortality at 12 months were lactate, bilirubin, PT ratio and age. The Child-Pugh + Lactate score was modified to produce an objective score comprising Albumin, Bilirubin and Clotting (PT ratio) added to serum lactate concentration in mmol L-1 (ABC + Lactate). This score was the best predictor of 12-month survival, with an AUC of 0.83. A proposed classification by ABC + Lactate score was highly significant (p = 0.001), with those in the highest class having ICU mortality of 75% and hospital and 12-month mortality of 93%. CONCLUSIONS Patients with cirrhosis admitted to ICU have high initial mortality but low mortality after hospital discharge. Child-Pugh class at ICU admission predicts outcome at 12 months. The ABC + Lactate classification system may be useful in identifying critically ill cirrhotic patients with very high long-term mortality.
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Affiliation(s)
- Alex Warren
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, Room 2.73, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
| | - Charlotte R. Soulsby
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, Room 2.73, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
| | - Alex Puxty
- Intensive Care Unit, NHS Greater Glasgow and Clyde, 84 Castle Street, Glasgow, Scotland G4 OSF UK
| | - Joseph Campbell
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, Room 2.73, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
| | - Martin Shaw
- Medical Physics, NHS Greater Glasgow and Clyde, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
| | - Tara Quasim
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, Room 2.73, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
- Intensive Care Unit, NHS Greater Glasgow and Clyde, 84 Castle Street, Glasgow, Scotland G4 OSF UK
| | - John Kinsella
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, Room 2.73, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
| | - Joanne McPeake
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, Room 2.73, Level 2, New Lister Building, Glasgow Royal Infirmary, 10-16 Alexandra Parade, Glasgow, Scotland G31 2ER UK
- Intensive Care Unit, NHS Greater Glasgow and Clyde, 84 Castle Street, Glasgow, Scotland G4 OSF UK
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Selden C, Bundy J, Erro E, Puschmann E, Miller M, Kahn D, Hodgson H, Fuller B, Gonzalez-Molina J, Le Lay A, Gibbons S, Chalmers S, Modi S, Thomas A, Kilbride P, Isaacs A, Ginsburg R, Ilsley H, Thomson D, Chinnery G, Mankahla N, Loo L, Spearman CW. A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure. Sci Rep 2017; 7:14518. [PMID: 29109530 PMCID: PMC5674071 DOI: 10.1038/s41598-017-15021-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 10/20/2017] [Indexed: 12/15/2022] Open
Abstract
Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions. The methodology has been designed to meet specifications for GMP production, required for manufacture of advanced therapy medicinal products (ATMPs). In a porcine model of severe liver failure, damage was assured in all animals by surgical ischaemia in pigs with human sized livers (1.2-1.6 kg liver weights). The BioArtificial liver (UCLBAL) improved important prognostic clinical liver-related parameters, eg, a significant improvement in coagulation, reduction in vasopressor requirements, improvement in blood pH and in parameters of intracranial pressure (ICP) and oxygenation.
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Affiliation(s)
- Clare Selden
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom.
| | - James Bundy
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Eloy Erro
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Eva Puschmann
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Malcolm Miller
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Delawir Kahn
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Humphrey Hodgson
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Barry Fuller
- Dept. of Surgery, UCL Medical School, Royal Free Hospital, London, NW3 2QG, UK
| | - Jordi Gonzalez-Molina
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Aurelie Le Lay
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Stephanie Gibbons
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Sherri Chalmers
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Sunil Modi
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Amy Thomas
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Peter Kilbride
- UCL Institute for Liver and Digestive Health, UCL - Royal Free Hospital Campus, UCL Medical School, London, United Kingdom
| | - Agnes Isaacs
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Richard Ginsburg
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Helen Ilsley
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - David Thomson
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Galya Chinnery
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Ncedile Mankahla
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - Lizel Loo
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
| | - C Wendy Spearman
- Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa
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El-Ghannam MT, Hassanien MH, El-Talkawy MD, Saleem AAA, Sabry AI, Abu Taleb HM. Performance of Disease-Specific Scoring Models in Intensive Care Patients with Severe Liver Diseases. J Clin Diagn Res 2017; 11:OC12-OC16. [PMID: 28764217 DOI: 10.7860/jcdr/2017/24543.9980] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 02/15/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Egypt has the highest prevalence of Hepatitis C Virus (HCV) in the world, estimated nationally at 14.7%. HCV treatment consumes 20% ($80 million) of Egypt's annual health budget. Outcomes of cirrhotic patients admitted to the ICU may, in fact, largely depend on differences in the state of the disease, criteria and indications for admission, resource utilization, and intensity of treatment. AIM The aim of the present study was to evaluate the efficacy of liver specific scoring models in predicting the outcome of critically ill cirrhotic patients in the ICU as it may help in prioritization of high risk patients and preservation of ICU resources. MATERIALS AND METHODS Over one year, a total of 777 patients with End Stage Liver Disease (ESLD) due to HCV infection were included in this retrospective non-randomized human study. All statistical analyses were performed by the statistical software SPSS version 22.0 (SPSS, Chicago, IL, USA). Child Turcotte Pugh (CTP) score, MELD score, MELD-Na, MESO, iMELD, Refit MELD and Refit MELD-Na were calculated on ICU admission. RESULTS ICU admission was mainly due to Gastrointestinal (GI) bleeding and Hepatic Encephalopathy (HE). Overall mortality was 27%. Age and sex showed no statistical difference between survivors and non survivors. Significantly higher mean values were observed for all models among individuals who died compared to survivors. MELD-Na was the most specific compared to the other scores. MELD-Na was highly predictive of mortality at an optimized cut-off value of 20.4 (AURC=0.789±0.03-CI 95%=0.711-0.865) while original MELD was highly predictive of mortality at an optimized cut-off value of 17.4 (AURC=0.678±0.01-CI 95%=0.613-0.682) denoting the importance of adding serum sodium to the original MELD. INR, serum creatinine, bilirubin, white blood cells count and hyponatremia were significantly higher in non survivors compared to survivors, while hypoalbuminemia showed no statistical difference. The advent of Hepatorenal Syndrome (HRS) and Spontaneous Bacterial Peritonitis (SBP) carried worse prognosis. Hyponatremia and number of transfused blood bags were additional independent predictors of mortality. CONCLUSION In cirrhosis of liver, due to HCV infection, patients who died during their ICU stay displayed significantly higher values on all prognostic scores at admission. The addition of sodium to MELD score greatly improves the predictive accuracy of mortality. MELD-Na showed the highest predictive value of all scores.
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Affiliation(s)
- Maged T El-Ghannam
- Professor, Department of Hepatogastroenterology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
| | - Moataz H Hassanien
- Professor, Department of Hepatogastroenterology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
| | - Mohamed D El-Talkawy
- Assistant Professor, Department of Hepatogastroenterology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
| | - Abdel Aziz A Saleem
- Assistant Professor, Department of Hepatogastroenterology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
| | - Amal I Sabry
- Lecturer, Department of Intensive Care, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
| | - Hoda M Abu Taleb
- Lecturer, Department of Biostatistics, Theodor Bilharz Research Institute (TBRI), Giza, Egypt
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Predicting mortality of patients with cirrhosis admitted to medical intensive care unit: An experience of a single tertiary center. Arab J Gastroenterol 2016; 17:159-163. [PMID: 27988236 DOI: 10.1016/j.ajg.2016.11.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 11/25/2016] [Accepted: 11/27/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND STUDY AIMS Prognosis for patients with cirrhosis admitted to a medical intensive care unit (MICU) is poor and no previous studies have been published from Qatar or other countries in the region to investigate this issue. The objective of this study was to assess the predictors for in-hospital mortality and admission of cirrhotic patients to MICU in a single tertiary hospital in Qatar. PATIENTS AND METHODS All adult cirrhotic MICU patients hospitalized from 2007 through 2012 to Hamad General Hospital-Qatar were included. We compared them to cirrhotic patients admitted to medical wards during same period of time. All data were recorded and analyzed with respect to demographic parameters, clinical features and laboratory as well as radiology characteristics on day one of admission to MICU. Cirrhosis diagnosis was established either with a liver biopsy or the combination of physical, laboratory and radiologic findings. Predictors of mortality were defined by logistic regression analysis. RESULTS The cohort comprised 109 cirrhotic MICU patients (86.2% males), and their mean age±SD was 51.6±11.5. MICU-cirrhotic patients had longer hospital stays than medical wards-cirrhotic patients (p=0.01). Admission with severe hepatic encephalopathy, upper gastrointestinal bleeding and SOFA (Sepsis Related Organ Failure Assessment) score were the independent predicting factors for MICU admission. Mortality was higher for the MICU-cirrhotic group than medical wards group (27 (24.8%) deaths vs. 12 (5.3%) deaths, respectively, p=0.001). In multivariate logistic regression analyses, older age>60years (p=0.04), APACH-II score (p=0.001) and MELD score (p=0.02) were independent predicting factors for overall mortality. CONCLUSION Severe hepatic encephalopathy, upper gastrointestinal bleeding and SOFA score predict MICU admission of cirrhotic patients. Among MICU cirrhotic patients, older age, APACH-II score and MELD score predict mortality.
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Annamalai A, Harada MY, Chen M, Tran T, Ko A, Ley EJ, Nuno M, Klein A, Nissen N, Noureddin M. Predictors of Mortality in the Critically Ill Cirrhotic Patient: Is the Model for End-Stage Liver Disease Enough? J Am Coll Surg 2016; 224:276-282. [PMID: 27887981 DOI: 10.1016/j.jamcollsurg.2016.11.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 10/26/2016] [Accepted: 11/15/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Critically ill cirrhotics require liver transplantation urgently, but are at high risk for perioperative mortality. The Model for End-stage Liver Disease (MELD) score, recently updated to incorporate serum sodium, estimates survival probability in patients with cirrhosis, but needs additional evaluation in the critically ill. The purpose of this study was to evaluate the predictive power of ICU admission MELD scores and identify clinical risk factors associated with increased mortality. STUDY DESIGN This was a retrospective review of cirrhotic patients admitted to the ICU between January 2011 and December 2014. Patients who were discharged or underwent transplantation (survivors) were compared with those who died (nonsurvivors). Demographic characteristics, admission MELD scores, and clinical risk factors were recorded. Multivariate regression was used to identify independent predictors of mortality, and measures of model performance were assessed to determine predictive accuracy. RESULTS Of 276 patients who met inclusion criteria, 153 were considered survivors and 123 were nonsurvivors. Survivor and nonsurvivor cohorts had similar demographic characteristics. Nonsurvivors had increased MELD, gastrointestinal bleeding, infection, mechanical ventilation, encephalopathy, vasopressors, dialysis, renal replacement therapy, requirement of blood products, and ICU length of stay. The MELD demonstrated low predictive power (c-statistic 0.73). Multivariate analysis identified MELD score (adjusted odds ratio [AOR] = 1.05), mechanical ventilation (AOR = 4.55), vasopressors (AOR = 3.87), and continuous renal replacement therapy (AOR = 2.43) as independent predictors of mortality, with stronger predictive accuracy (c-statistic 0.87). CONCLUSIONS The MELD demonstrated relatively poor predictive accuracy in critically ill patients with cirrhosis and might not be the best indicator for prognosis in the ICU population. Prognostic accuracy is significantly improved when variables indicating organ support (mechanical ventilation, vasopressors, and continuous renal replacement therapy) are included in the model.
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Affiliation(s)
| | - Megan Y Harada
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Melissa Chen
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Tram Tran
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Ara Ko
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Eric J Ley
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Miriam Nuno
- Center for Neurosurgical Outcomes Research, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Andrew Klein
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Nicholas Nissen
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Mazen Noureddin
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
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Taghipour M, Eftekhari G, Haddadian Z, Mazloom R, Mani M, Mani AR. Increased sample asymmetry and memory of cardiac time-series following endotoxin administration in cirrhotic rats. Physiol Meas 2016; 37:N96-N104. [DOI: 10.1088/0967-3334/37/11/n96] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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O'Brien A, China L, Massey KA, Nicolaou A, Winstanley A, Newson J, Hobbs A, Audzevich T, Gilroy DW. Bile duct-ligated mice exhibit multiple phenotypic similarities to acute decompensation patients despite histological differences. Liver Int 2016; 36:837-46. [PMID: 26012885 PMCID: PMC4869675 DOI: 10.1111/liv.12876] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 05/13/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Patients with decompensated cirrhosis are susceptible to infection. Innate immune dysfunction and development of organ failure are considered to underlie this. A rodent model of liver disease sharing these phenotypic features would assist in vivo study of underlying mechanisms and testing of therapeutics. We evaluated three models to identify which demonstrated the greatest clinical and immunological phenotypic similarity to patients with acutely decompensated (AD) cirrhosis. METHODS We selected Bile Duct Ligation (BDL) rats at 4 weeks, BDL mice at 14 days and Carbon tetrachloride (CCl4 ) mice at 10 weeks (with studies performed 7 days after final CCl4 infection). We examined organ dysfunction, inflammatory response to carrageenan-in-paw, plasma eicosanoid concentrations, macrophage cytokine production and responses to peritoneal infection. RESULTS Bile duct ligation caused sarcopenia, liver, cardiovascular and renal dysfunction whereas CCl4 mice demonstrated no clinical abnormalities. BDL rodents exhibited depressed response to carrageenan-in-paw unlike CCl4 mice. BDL rats have slightly elevated plasma eicosanoid levels and plasma showed partial PGE2 -mediated immune suppression whereas CCl4 mice did not. Plasma NOx was elevated in patients with acute or chronic liver failure (AoCLF) compared to healthy volunteers and BDL rodents but not CCl4 mice. Elevated nitric oxide (NO) via inducible nitric oxide synthase (iNOS) mediates defective leucocyte trafficking in BDL rodent models. CONCLUSIONS We conclude that BDL mice and rats are not simply models of cholestatic liver injury but may be used to study mechanisms underlying poor outcome from infection in AD and have identified elevated NO as a potential mediator of depressed leucocyte trafficking.
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Affiliation(s)
- Alastair O'Brien
- Centre for Clinical Pharmacology and TherapeuticsDivision of MedicineUniversity College LondonLondonUK
| | - Louise China
- Centre for Clinical Pharmacology and TherapeuticsDivision of MedicineUniversity College LondonLondonUK
| | - Karen A. Massey
- Manchester Pharmacy SchoolFaculty of Medical and Human Sciencesthe University of ManchesterManchesterUK
| | - Anna Nicolaou
- Manchester Pharmacy SchoolFaculty of Medical and Human Sciencesthe University of ManchesterManchesterUK
| | - Alison Winstanley
- Department of HistopathologyUniversity College London HospitalsLondonUK
| | - Justine Newson
- Centre for Clinical Pharmacology and TherapeuticsDivision of MedicineUniversity College LondonLondonUK
| | | | - Tatsiana Audzevich
- Centre for Clinical Pharmacology and TherapeuticsDivision of MedicineUniversity College LondonLondonUK
| | - Derek W. Gilroy
- Manchester Pharmacy SchoolFaculty of Medical and Human Sciencesthe University of ManchesterManchesterUK
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China L, Muirhead N, Skene SS, Shabir Z, PH De Maeyer R, Maini AAN, W Gilroy D, J O'Brien A. ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial. BMJ Open 2016; 6:e010132. [PMID: 26810999 PMCID: PMC4735307 DOI: 10.1136/bmjopen-2015-010132] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds and inactivates this hormone. Human albumin solution could thus be repurposed as an immune restorative drug in these patients.This feasibility study aims to determine whether it is possible and safe to restore serum albumin to >30 g/L and maintain it at this level in patients admitted with acute decompensated cirrhosis using repeated 20% human albumin infusions according to daily serum albumin levels. METHODS AND ANALYSIS Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) stage 1 is a multicentre, open label dose feasibility trial. Patients with acutely decompensated cirrhosis admitted to hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Daily intravenous human albumin solution will be infused, according to serum albumin levels, for up to 14 days or discharge in all patients. The primary end point is daily serum albumin levels for the duration of the treatment period and the secondary end point is plasma-induced macrophage dysfunction. The trial will recruit 80 patients. Outcomes will be used to assist with study design for an 866 patient randomised controlled trial at more than 30 sites across the UK. ETHICS AND DISSEMINATION Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). RESULTS Will be disseminated through peer reviewed journals and international conferences. Recruitment of the first participant occurred on 26/05/2015. TRIAL REGISTRATION NUMBER The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the NIHR (ISRCTN 14174793). This manuscript refers to V.4.0 of the protocol; Pre-results.
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Affiliation(s)
- Louise China
- Division of Medicine, University College London (UCL), London, UK
| | - Nicola Muirhead
- Comprehensive Clinical Trials Unit, University College London (UCL), London, UK
| | - Simon S Skene
- Comprehensive Clinical Trials Unit, University College London (UCL), London, UK
| | - Zainib Shabir
- Comprehensive Clinical Trials Unit, University College London (UCL), London, UK
| | | | | | - Derek W Gilroy
- Division of Medicine, University College London (UCL), London, UK
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Fernández J, Aracil C, Solà E, Soriano G, Cinta Cardona M, Coll S, Genescà J, Hombrados M, Morillas R, Martín-Llahí M, Pardo A, Sánchez J, Vargas V, Xiol X, Ginès P. [Evaluation and treatment of the critically ill cirrhotic patient]. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:607-626. [PMID: 26778768 DOI: 10.1016/j.gastrohep.2015.09.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 09/15/2015] [Accepted: 09/18/2015] [Indexed: 12/12/2022]
Abstract
Cirrhotic patients often develop severe complications requiring ICU admission. Grade III-IV hepatic encephalopathy, septic shock, acute-on-chronic liver failure and variceal bleeding are clinical decompensations that need a specific therapeutic approach in cirrhosis. The increased effectiveness of the treatments currently used in this setting and the spread of liver transplantation programs have substantially improved the prognosis of critically ill cirrhotic patients, which has facilitated their admission to critical care units. However, gastroenterologists and intensivists have limited knowledge of the pathogenesis, diagnosis and treatment of these complications and of the prognostic evaluation of critically ill cirrhotic patients. Cirrhotic patients present alterations in systemic and splanchnic hemodynamics, coagulation and immune dysfunction what further increase the complexity of the treatment, the risk of developing new complications and mortality in comparison with the general population. These differential characteristics have important diagnostic and therapeutic implications that must be known by general intensivists. In this context, the Catalan Society of Gastroenterology and Hepatology requested a group of experts to draft a position paper on the assessment and treatment of critically ill cirrhotic patients. This article describes the recommendations agreed upon at the consensus meetings and their main conclusions.
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Affiliation(s)
- Javier Fernández
- Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERehd, Barcelona, España
| | - Carles Aracil
- Servei de Digestiu, Hospital Universitari Arnau de Villanova, Lleida, España
| | - Elsa Solà
- Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERehd, Barcelona, España
| | - Germán Soriano
- Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau. CIBERehd, Instituto de Salud Carlos III, Barcelona, España
| | - Maria Cinta Cardona
- Servicio de Digestivo, Hospital de Tortosa Verge de la Cinta, Tortosa, Tarragona, España
| | - Susanna Coll
- Servicio de Digestivo, Hospital del Mar, Barcelona, España
| | - Joan Genescà
- Servicio de Medicina Interna-Hepatología, Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron (VHIR), Universidad Autónoma de Barcelona CIBERehd, Barcelona, España
| | - Manoli Hombrados
- Servicio de Aparato Digestivo, Hospital Dr. Josep Trueta, Facultat de Medicina, Universitat de Girona, Girona, España
| | - Rosa Morillas
- Servicio de Hepatología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España
| | - Marta Martín-Llahí
- Servei de Digestiu, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, España
| | - Albert Pardo
- Servicio de Aparato Digestivo, Hospital Universitari de Tarragona Joan XXIII, Tarragona, España
| | - Jordi Sánchez
- Corporació Sanitària Parc Taulí, Sabadell. CIBERehd, Instituto de Salud Carlos III, Sabadell, Barcelona, España
| | - Victor Vargas
- Servicio de Medicina Interna-Hepatología, Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron (VHIR), Universidad Autónoma de Barcelona CIBERehd, Barcelona, España
| | - Xavier Xiol
- Servicio de Aparato Digestivo, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, España
| | - Pere Ginès
- Liver Unit, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERehd, Barcelona, España.
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Coudroy R, Jamet A, Thille AW. Is skin mottling a predictor of high mortality in non-selected patients with cirrhosis admitted to intensive care unit? J Hepatol 2015; 63:770-1. [PMID: 26055801 DOI: 10.1016/j.jhep.2015.05.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Accepted: 05/04/2015] [Indexed: 01/09/2023]
Affiliation(s)
- Rémi Coudroy
- CHU de Poitiers, Service de Réanimation Médicale, Poitiers, France; CIC 1402 (ALIVE group), Université de Poitiers, Poitiers, France.
| | - Angéline Jamet
- CHU de Poitiers, Service de Réanimation Médicale, Poitiers, France
| | - Arnaud W Thille
- CHU de Poitiers, Service de Réanimation Médicale, Poitiers, France; CIC 1402 (ALIVE group), Université de Poitiers, Poitiers, France
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Ghabril M. Improving Outcomes in Critical Care of Patients With Cirrhosis and Organ Failure: Herding Runaway Horses and Securing the Barn Door. Clin Gastroenterol Hepatol 2015; 13:1361-3. [PMID: 25681692 DOI: 10.1016/j.cgh.2015.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 02/06/2015] [Accepted: 02/08/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
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Artru F, Louvet A. Admission des patients cirrhotiques en réanimation : le score de Child-Pugh est-il un outil pertinent ? ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s13546-015-1079-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Karvellas CJ, Abraldes JG, Arabi YM, Kumar A. Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study. Aliment Pharmacol Ther 2015; 41:747-57. [PMID: 25703246 DOI: 10.1111/apt.13135] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 12/19/2014] [Accepted: 02/02/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP)-associated septic shock carries significant mortality in cirrhosis. AIM To determine whether practice-related aspects of antimicrobial therapy contribute to high mortality. METHODS Retrospective cohort study of all (n = 126) cirrhotics with spontaneous bacterial peritonitis (neutrophil count >250 or positive ascitic culture)-associated septic shock (1996-2011) from an international, multicenter database. Appropriate antimicrobial therapy implied either in vitro activity against a subsequently isolated pathogen (culture positive) or empiric management consistent with broadly accepted norms (culture negative). RESULTS Overall hospital mortality was 81.8%. Comparing survivors (n = 23) with non-survivors (n = 103), survivors had lower Acute Physiology and Chronic Health Evaluation (APACHEII) (mean ± s.d.; 22 ± 7 vs. 32 ± 8) and model for end-stage liver disease (MELD) (24 ± 9 vs. 34 ± 11) scores and serum lactate on admission (4.9 ± 3.1 vs. 8.9 ± 5.3), P < 0.001 for all. Survivors were less likely to receive inappropriate initial antimicrobial therapy (0% vs. 25%, P = 0.013) and received appropriate antimicrobial therapy earlier [median 1.8 (1.1-5.2) vs. 9.5 (3.9-14.3) h, P < 0.001]. After adjusting for covariates, APACHEII [OR, odds ratio 1.45 (1.04-2.02) per 1 unit increment, P = 0.03], lactate [OR 2.34 (1.04-5.29) per unit increment, P = 0.04] and time delay to appropriate antimicrobials [OR 1.86 (1.10-3.14) per hour increment, P = 0.02] were significantly associated with increased mortality. CONCLUSIONS Cirrhotic patients with septic shock secondary to spontaneous bacterial peritonitis have high mortality (>80%). Each hour of delay in appropriate antimicrobial therapy was associated with a 1.86 times increased hospital mortality. Admission APACHEII and serum lactate also significantly impacted hospital mortality. Earlier initiation of appropriate antimicrobial therapy could substantially improve outcome.
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Affiliation(s)
- C J Karvellas
- Division of Critical Care Medicine and Gastroenterology/Hepatology, University of Alberta, Edmonton, AB, Canada; Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, AB, Canada
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Ostadhadi S, Rezayat SM, Ejtemaei-Mehr S, Tavangar SM, Nikoui V, Jazaeri F, Eftekhari G, Abdollahi A, Dehpour AR. Mesenteric artery responsiveness to acetylcholine and phenylephrine in cirrhotic rats challenged with endotoxin: the role of TLR4. Can J Physiol Pharmacol 2015; 93:475-83. [PMID: 25978623 DOI: 10.1139/cjpp-2014-0515] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Cirrhosis is associated with vascular dysfunction and endotoxemia. These experiments were designed to investigate the hypothesis that the administration of a low-dose of lipopolysaccharide (LPS) worsens vascular dysfunction in rats subjected to bile-duct ligation (BDL), and to determine whether LPS initiates changes in vascular Toll-like receptor 4 (TLR4) expression. Four weeks after BDL, the animals were given an intraperitoneal injection of either saline or LPS (1.0 mg/kg body mass). Three hours later, the superior mesenteric artery was isolated, perfused, and then subjected to the vasoconstriction and vasodilatation effects of phenylephrine and acetylcholine, respectively. Our results show that phenylephrine-induced vasoconstriction decreased in the cirrhotic vascular bed (BDL rats) compared with the vascular bed of the sham-operated animals, and that the LPS injections in the cirrhotic (BDL) rats worsened this response. LPS injection administered to the sham-operated animals had no such effect. On the other hand, both the BDL procedure and the LPS injection increased acetylcholine-induced vasorelaxation, but LPS administration to the BDL rats had no effect on this response. The mRNA levels of TLR4 did not change, but immunohistochemical studies showed that TLR4 localization switched from the endothelium to vascular smooth muscle cells following chronic BDL. In conclusion, acute endotoxemia in cirrhotic rats is associated with hyporesponsiveness to phenylephrine and tolerance to the effects of acetylcholine. Altered localization of TLR4 may be responsible for these effects.
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Affiliation(s)
- Sattar Ostadhadi
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Fröhlich S, Murphy N, Kong T, Ffrench-O’Carroll R, Conlon N, Ryan D, Boylan J. Alcoholic liver disease in the intensive care unit: Outcomes and predictors of prognosis. J Crit Care 2014; 29:1131.e7-1131.e13. [DOI: 10.1016/j.jcrc.2014.06.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Revised: 06/02/2014] [Accepted: 06/02/2014] [Indexed: 12/14/2022]
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Williams R, Aspinall R, Bellis M, Camps-Walsh G, Cramp M, Dhawan A, Ferguson J, Forton D, Foster G, Gilmore I, Hickman M, Hudson M, Kelly D, Langford A, Lombard M, Longworth L, Martin N, Moriarty K, Newsome P, O'Grady J, Pryke R, Rutter H, Ryder S, Sheron N, Smith T. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014; 384:1953-97. [PMID: 25433429 DOI: 10.1016/s0140-6736(14)61838-9] [Citation(s) in RCA: 444] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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