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Lian H, Cai H, Wang X, Zhang H, Gao Y, Zhang S, Zhang Y. Inflammation-Associated Coagulation Reactions are Associated with the Prognosis in Critically Ill Very Old Patients (VOPs) with Infection. J Inflamm Res 2024; 17:9335-9346. [PMID: 39588142 PMCID: PMC11586478 DOI: 10.2147/jir.s474990] [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: 04/22/2024] [Accepted: 11/12/2024] [Indexed: 11/27/2024] Open
Abstract
Background Dysregulated host response is an important cause of critical illness. Coagulation reaction is the most primitive response and can be used to assess patient status. Coagulation reactions may be amplified in very old patients (VOPs). This study aimed to demonstrate coagulation reactions in critically ill VOPs by linking cytokines, coagulation, and fibrinolytic processes. Methods We analyzed 33 critically ill VOPs admitted to our hospital, with an average age of 91.97. Laboratory test results were collected and double checked. In-hospital mortality, Intensive Care Unit (ICU) stay, and length of in-hospital stay (LOS)-associated variables were assessed using a generalized additive mix model. Smooth curves and interaction tests were used to quantify statistical interactions. Results The in-hospital mortality rate was 45.5% in this study. The D-dimer level was correlated with ICU stay [risk ratio (RR), 1.39; 95% confidential interval (CI), 1.16-1.67] and LOS (RR, 1.75; 95% CI, 1.19-2.57). Other function or quantity indices, such as platelet (PLT), prothrombin time (PT), activated partial prothrombin time (APTT), and thrombomodulin (TM), were all correlated with clinical outcomes. After the link between coagulation reaction and the outcomes was constructed, it was revealed that, compared to lower level of IL-6, under high level of IL-6, elevated TM was likely to be associated with tissue plasminogen activator inhibitor complex (t-PAIC) elevation, which probably promoted the production of D-dimer (RR, 3.216; 95% CI, 1.840-4.592). Conclusion D-dimer levels are associated with outcomes in VOPs with critical illness. There is a certain link between inflammatory cytokines and the coagulation process. Under high IL-6 levels, the elevated TM may contribute to the increased t-PAIC, which contributes to the higher D-dimer level. Conversely, under low IL-6 levels, elevated TM levels are associated with reduced t-PAIC levels.
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Affiliation(s)
- Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Huacong Cai
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Xiaoting Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Hongmin Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Yuan Gao
- Department of Information Technology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Shuyang Zhang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China
| | - Yan Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
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Abdelrazic MI, Abdel Hakeem GL, Hanna MS, Mohamed OM, Ismail DE, Abuelela IS. Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Predictor for Sepsis Mortality in Children Admitted to Pediatric Intensive Care Unit (PICU): A Comparison With Prothrombin Time/International Normalized Ratio (PT/INR) and Urea/Creatinine Ratio. Cureus 2024; 16:e72643. [PMID: 39610635 PMCID: PMC11604251 DOI: 10.7759/cureus.72643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2024] [Indexed: 11/30/2024] Open
Abstract
Background Sepsis is the primary cause of death in children, and it is crucial to identify patients at high risk of mortality early on in order to provide intensive monitoring and management in the Pediatric Intensive Care Unit (PICU). Objective The objective of this study was to assess the predictive value of routinely used sepsis indicators, including neutrophil gelatinase-associated lipocalin (NGAL), urea to creatinine ratio (urea/Cr), and prothrombin time and international normalized ratio (PT/INR), in predicting death in critically unwell children. Patients and methods A total of 75 children were included in the research conducted at the PICU of Minia University. Among them, 21 (28%) were released as survivors, while the remaining 54 (72%) unfortunately passed away. All participating children were subjected to serum NGAL, urea/Cr, and PT/INR measurements during the first 24 hours of hospitalization. The severity of sepsis was assessed using the Pediatric Risk of Mortality (PRISM) III score. Results The NGAL, prothrombin, urea, and creatinine levels were considerably elevated in the group of individuals who died compared to those who survived (P < 0.001, 0.007, 0.028, and 0.032, respectively). However, no significant difference was found between survivors and deceased children in terms of the PT/INR ratio and urea/Cr ratio. When predicting mortality, NGAL with a cutoff point of more than 990 had a sensitivity of 100% and a specificity of 35%. Similarly, the PRISM score with a cutoff point greater than 18 had a sensitivity of 83.3% and a specificity of 42.9%. Conclusion Serum NGAL is reliable in the early prediction of mortality in children admitted with sepsis.
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Affiliation(s)
| | | | | | - Omima M Mohamed
- Clinical Pathology, Faculty of Medicine, Minia University, Minya, EGY
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3
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Cajander S, Kox M, Scicluna BP, Weigand MA, Mora RA, Flohé SB, Martin-Loeches I, Lachmann G, Girardis M, Garcia-Salido A, Brunkhorst FM, Bauer M, Torres A, Cossarizza A, Monneret G, Cavaillon JM, Shankar-Hari M, Giamarellos-Bourboulis EJ, Winkler MS, Skirecki T, Osuchowski M, Rubio I, Bermejo-Martin JF, Schefold JC, Venet F. Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine. THE LANCET. RESPIRATORY MEDICINE 2024; 12:305-322. [PMID: 38142698 DOI: 10.1016/s2213-2600(23)00330-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 08/14/2023] [Accepted: 08/24/2023] [Indexed: 12/26/2023]
Abstract
Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes.
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Affiliation(s)
- Sara Cajander
- Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Matthijs Kox
- Department of Intensive Care Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Brendon P Scicluna
- Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei hospital, University of Malta, Msida, Malta; Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Raquel Almansa Mora
- Department of Cell Biology, Genetics, Histology and Pharmacology, University of Valladolid, Valladolid, Spain
| | - Stefanie B Flohé
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Ignacio Martin-Loeches
- St James's Hospital, Dublin, Ireland; Hospital Clinic, Institut D'Investigacions Biomediques August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain
| | - Gunnar Lachmann
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine, Berlin, Germany
| | - Massimo Girardis
- Department of Intensive Care and Anesthesiology, University Hospital of Modena, Modena, Italy
| | - Alberto Garcia-Salido
- Hospital Infantil Universitario Niño Jesús, Pediatric Critical Care Unit, Madrid, Spain
| | - Frank M Brunkhorst
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
| | - Michael Bauer
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany
| | - Antoni Torres
- Pulmonology Department. Hospital Clinic of Barcelona, University of Barcelona, Ciberes, IDIBAPS, ICREA, Barcelona, Spain
| | - Andrea Cossarizza
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Guillaume Monneret
- Immunology Laboratory, Hôpital E Herriot - Hospices Civils de Lyon, Lyon, France; Université Claude Bernard Lyon-1, Hôpital E Herriot, Lyon, France
| | | | - Manu Shankar-Hari
- Centre for Inflammation Research, Institute of Regeneration and Repair, The University of Edinburgh, Edinburgh, UK
| | | | - Martin Sebastian Winkler
- Department of Anesthesiology and Intensive Care, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Tomasz Skirecki
- Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Marcin Osuchowski
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Vienna, Austria
| | - Ignacio Rubio
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany
| | - Jesus F Bermejo-Martin
- Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; School of Medicine, Universidad de Salamanca, Salamanca, Spain; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
| | - Joerg C Schefold
- Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Fabienne Venet
- Immunology Laboratory, Hôpital E Herriot - Hospices Civils de Lyon, Lyon, France; Centre International de Recherche en Infectiologie, Inserm U1111, CNRS, UMR5308, Ecole Normale Supeérieure de Lyon, Universiteé Claude Bernard-Lyon 1, Lyon, France.
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Zhu C, Hou Z, Zhu R, Zhou B, Sun Y, Li Z, Li X, Ding R, Luan Z, Liang Y, Wang L, Ma X. Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study. Surgery 2023; 173:1303-1310. [PMID: 36774318 DOI: 10.1016/j.surg.2023.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 12/11/2022] [Accepted: 01/06/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND A blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. METHODS Adult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18-64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. RESULTS Of the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. CONCLUSION Elderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.
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Affiliation(s)
- Chengrui Zhu
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhenzhen Hou
- Department of Surgical Intensive Care Unit, Beijing Chaoyang Hospital Affiliated to Capital Medical University, China
| | - Ran Zhu
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Baosen Zhou
- Department of Clinical Epidemiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yini Sun
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhiliang Li
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xu Li
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Renyu Ding
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhenggang Luan
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yingjian Liang
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Liang Wang
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xiaochun Ma
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.
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Histone Citrullination Mediates a Protective Role in Endothelium and Modulates Inflammation. Cells 2022; 11:cells11244070. [PMID: 36552833 PMCID: PMC9777278 DOI: 10.3390/cells11244070] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/10/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
NETosis is a key host immune process against a pathogenic infection during innate immune activation, consisting of a neutrophil "explosion" and, consequently, NET formation, containing mainly DNA, histones, and other nuclear proteins. During sepsis, an exacerbated immune host response to an infection occurs, activating the innate immunity and NETosis events, which requires histone H3 citrullination. Our group compared the circulating histone levels with those citrullinated H3 levels in plasma samples of septic patients. In addition, we demonstrated that citrullinated histones were less cytotoxic for endothelial cells than histones without this post-translational modification. Citrullinated histones did not affect cell viability and did not activate oxidative stress. Nevertheless, citrullinated histones induced an inflammatory response, as well as regulatory endothelial mechanisms. Furthermore, septic patients showed elevated levels of circulating citrullinated histone H3, indicating that the histone citrullination is produced during the first stages of sepsis, probably due to the NETosis process.
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de Andrade SA, de Souza DA, Torres AL, de Lima CFG, Ebram MC, Celano RMG, Schattner M, Chudzinski-Tavassi AM. Pathophysiology of COVID-19: Critical Role of Hemostasis. Front Cell Infect Microbiol 2022; 12:896972. [PMID: 35719336 PMCID: PMC9205169 DOI: 10.3389/fcimb.2022.896972] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 05/05/2022] [Indexed: 12/18/2022] Open
Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.
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Affiliation(s)
| | | | | | | | | | | | - Mirta Schattner
- Laboratory of Experimental Thrombosis. Instituto de Medicina Experimental – CONICET -Academia Nacional de Medicina, Buenos Aires, Argentina
| | - Ana Marisa Chudzinski-Tavassi
- Center of Excellence in New Target Discovery (CENTD), Instituto Butantan, São Paulo, Brazil
- Innovation and Development Laboratory, Instituto Butantan, São Paulo, São Paulo, Brazil
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Hematologic System Dysregulation in Critically Ill Septic Patients with Anemia-A Retrospective Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19116626. [PMID: 35682209 PMCID: PMC9180773 DOI: 10.3390/ijerph19116626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/19/2022] [Accepted: 05/27/2022] [Indexed: 11/29/2022]
Abstract
Sepsis can affect various organs as well as the hematologic system. Systemic dysregulation, present in sepsis, affects particularly red blood cells (RBCs). One of the widely available RBC indices is RBC distribution width (RDW). Sepsis may also affect hemostasis, with septic patients presenting with coagulopathy or disseminated intravascular coagulation. The aim of our study was to analyze the impact of sepsis on RBC indices and coagulation parameters on admission to the intensive care unit (ICU) and their association with presence of sepsis and sepsis outcomes in anemic critically ill patients. We performed a retrospective observational study covering consecutive patients admitted to a 10-bed mixed ICU in the years 2020−2021. We found significant differences between septic and non-septic patients for the following parameters: RDW (p = 0.02), INR (p < 0.01), aPTT (p < 0.01), D-dimers (p < 0.01), fibrinogen (p = 0.02), platelets (p = 0.04). International normalized ratio was the only parameter with adequate sepsis predictive value (AUROC = 0.70; 95% CI 0.63−0.76; p < 0.01), with an optimal cut-off value of >1.21. Combination of INR with fibrinogen and a severity of disease score improved INR’s predictive value (AUROC 0.74−0.77). Combination of INR with a severity of disease score was an adequate ICU mortality predictor in septic patients (AUROC 0.70−0.75). Sepsis significantly affects RDW and most coagulation parameters. Increased INR can be used for sepsis screening, whereas combination of INR with a severity of disease score can be a predictor of short-term mortality in septic patients.
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Biomarkers Predicting Tissue Pharmacokinetics of Antimicrobials in Sepsis: A Review. Clin Pharmacokinet 2022; 61:593-617. [PMID: 35218003 PMCID: PMC9095522 DOI: 10.1007/s40262-021-01102-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2021] [Indexed: 02/07/2023]
Abstract
The pathophysiology of sepsis alters drug pharmacokinetics, resulting in inadequate drug exposure and target-site concentration. Suboptimal exposure leads to treatment failure and the development of antimicrobial resistance. Therefore, we seek to optimize antimicrobial therapy in sepsis by selecting the right drug and the correct dosage. A prerequisite for achieving this goal is characterization and understanding of the mechanisms of pharmacokinetic alterations. However, most infections take place not in blood but in different body compartments. Since tissue pharmacokinetic assessment is not feasible in daily practice, we need to tailor antibiotic treatment according to the specific patient’s pathophysiological processes. The complex pathophysiology of sepsis and the ineffectiveness of current targeted therapies suggest that treatments guided by biomarkers predicting target-site concentration could provide a new therapeutic strategy. Inflammation, endothelial and coagulation activation markers, and blood flow parameters might be indicators of impaired tissue distribution. Moreover, hepatic and renal dysfunction biomarkers can predict not only drug metabolism and clearance but also drug distribution. Identification of the right biomarkers can direct drug dosing and provide timely feedback on its effectiveness. Therefore, this might decrease antibiotic resistance and the mortality of critically ill patients. This article fills the literature gap by characterizing patient biomarkers that might be used to predict unbound plasma-to-tissue drug distribution in critically ill patients. Although all biomarkers must be clinically evaluated with the ultimate goal of combining them in a clinically feasible scoring system, we support the concept that the appropriate biomarkers could be used to direct targeted antibiotic dosing.
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Juschten J, Bos LDJ, de Grooth HJ, Beuers U, Girbes ARJ, Juffermans NP, Loer SA, van der Poll T, Cremer OL, Bonten MJM, Schultz MJ, Tuinman PR. Incidence, Clinical Characteristics and Outcomes of Early Hyperbilirubinemia in Critically Ill Patients: Insights From the MARS Study. Shock 2022; 57:161-167. [PMID: 34238904 PMCID: PMC8757589 DOI: 10.1097/shk.0000000000001836] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/19/2021] [Accepted: 06/29/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To investigate the incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients. DESIGN AND SETTING This is a post hoc analysis of a prospective multicenter cohort study. PATIENTS Patients with measured bilirubin levels within the first 2 days after ICU admission were eligible. Patients with liver cirrhosis were excluded. ENDPOINTS The primary endpoint was the incidence of early hyperbilirubinemia, defined as bilirubin ≥33 μmol/L within 2 days after ICU admission. Secondary endpoints included clinical characteristics of patients with versus patients without early hyperbilirubinemia, and outcomes up to day 30. RESULTS Of 4,836 patients, 559 (11.6%) patients had early hyperbilirubinemia. Compared to patients without early hyperbilirubinemia, patients with early hyperbilirubinemia presented with higher severity of illness scores, and higher incidences of sepsis and organ failure. After adjustment for confounding variables, early hyperbilirubinemia remained associated with mortality at day 30 (odds ratio, 1.31 [95%-confidence interval 1.06-1.60]; P = 0.018). Patients with early hyperbilirubinemia and thrombocytopenia (interaction P-value = 0.005) had a higher likelihood of death within 30 days (odds ratio, 2.61 [95%-confidence interval 2.08-3.27]; P < 0.001) than patients with early hyperbilirubinemia and a normal platelet count (odds ratio, 1.09 [95%-confidence interval 0.75-1.55]; P = 0.655). CONCLUSIONS Early hyperbilirubinemia occurs frequently in the critically ill, and these patients present with higher disease severity and more often with sepsis and organ failures. Early hyperbilirubinemia has an association with mortality, albeit this association was only found in patients with concomitant thrombocytopenia.
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Affiliation(s)
- Jenny Juschten
- Department of Anesthesiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Lieuwe D. J. Bos
- Department of Intensive Care, Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands
- Department of Pulmonology, Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands
| | - Harm-Jan de Grooth
- Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands
| | - Armand R. J. Girbes
- Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Nicole P. Juffermans
- Department of Intensive Care Medicine, OLVG Hospital, Amsterdam, The Netherlands
| | - Stephan A. Loer
- Department of Anesthesiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Tom van der Poll
- Division of Infectious Diseases, Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands
| | - Olaf L. Cremer
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marc J. M. Bonten
- Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marcus J. Schultz
- Department of Intensive Care, Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands
- Mahidol–Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Pieter Roel Tuinman
- Department of Intensive Care, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Research VUmc Intensive Care (REVIVE), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Mohsin M, Farooq MU, Akhtar W, Mustafa W, Rehman TU, Malik J, Zahid T. Echocardiography in a critical care unit: A contemporary review. Expert Rev Cardiovasc Ther 2022; 20:55-63. [PMID: 35098852 DOI: 10.1080/14779072.2022.2036124] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Echocardiography is a rapid, noninvasive, and complete cardiac assessment tool for patients with hemodynamic instability. This review provides an overview of the evidence for current practices in critical care units (CCUs), incorporating the use of echocardiography in different etiologies of shock. AREAS COVERED : Relevant articles were extracted after searching on databases by two reviewers and incorporated in this review in a narrative style. EXPERT OPINION : In an acute scenario, a basic echocardiographic study yields prompt diagnosis, allowing for the initiation of treatment. The most common pathologies in shocked patients are identified promptly using two-dimensional (2D) and M-mode echocardiography. A more comprehensive assessment can follow after patients have been stabilized. There are four types of shock: (i) cardiogenic shock, (ii) hypovolemic shock, (iii) obstructive shock, and (iv) septic shock. All of them can be readily identified by echocardiography. As echocardiography is increasingly being used in an intensive care setting, its applications and evidence base should be expanded by randomized controlled trials to demonstrate patient outcomes in critical care.
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Affiliation(s)
- Muhammad Mohsin
- Department of Interventional Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi, 46000, Pakistan
| | - Muhammad Umar Farooq
- Department of Interventional Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi, 46000, Pakistan
| | - Waheed Akhtar
- Department of Cardiology, Abbas Institute of Medical Sciences, Muzaffarabad, 13190, Pakistan
| | - Waqar Mustafa
- Department of Cardiology, Abbas Institute of Medical Sciences, Muzaffarabad, 13190, Pakistan
| | - Tanzeel Ur Rehman
- Department of Cardiology, Benazir Bhutto Hospital, Rawalpindi, 46000, Pakistan
| | - Jahanzeb Malik
- Department of Interventional Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi, 46000, Pakistan
| | - Taimoor Zahid
- Department of Medicine, Warwick Hospital, Warwickshire, United Kingdom
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Pravda J. Sepsis: Evidence-based pathogenesis and treatment. World J Crit Care Med 2021; 10:66-80. [PMID: 34316443 PMCID: PMC8291008 DOI: 10.5492/wjccm.v10.i4.66] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/13/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H2O2), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H2O2 can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H2O2 is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H2O2 mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H2O2 have been reported in patients with septic shock. This review provides evidence to support a causal role for H2O2 in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H2O2 levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness.
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Affiliation(s)
- Jay Pravda
- Inflammatory Disease Research Centre, Therashock LLC, Palm Beach Gardens, FL 33410, United States
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