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Bottari G, Ranieri VM, Ince C, Pesenti A, Aucella F, Scandroglio AM, Ronco C, Vincent JL. Use of extracorporeal blood purification therapies in sepsis: the current paradigm, available evidence, and future perspectives. Crit Care 2024; 28:432. [PMID: 39722012 PMCID: PMC11670469 DOI: 10.1186/s13054-024-05220-7] [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: 10/11/2024] [Accepted: 12/16/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Sepsis is the result of a dysregulated immune response to infection and is associated with acute organ dysfunction. The syndrome's complexity is contingent upon the underlying pathology and individual patient characteristics, including their immune response. The involvement of multiple organs and physiological functions adds complexity, with "organ cross-talk" emerging as a pivotal pathophysiological and clinical aspect. This narrative review to evaluate the rationale and available clinical evidence supporting the use of extracorporeal blood purification therapies as adjunctive therapy in patients with sepsis and septic shock. MAIN BODY A search of the PubMed, Embase, Web of Science and Scopus databases for relevant literature from August 2002 to May 2024 has been conducted. The search was performed using the terms: 1) "blood purification" or "hemadsorption" or "plasma exchange" AND 2) "sepsis" or "septic shock". Therefore the authors have focused our discussion on several key areas such as conducting well-designed trials, developing more personalized protocols, ensuring optimal management and monitoring. CONCLUSIONS Given the heterogeneity of patients with sepsis, conducting traditional randomized clinical trials in this domain can be a daunting task. However, statistical techniques such as Bayesian methods, propensity score analysis, and emulated clinical trials using clinical databases hold promise for enhancing comparability between the study groups. Indeed, to comprehend the clinical efficacy of extracorporeal blood purification techniques in patients with sepsis, it is imperative to assemble homogeneous groups of patients receiving uniform treatments. Clinical strategies should be individualized, signaling the end of the "one size fits all" approach in sepsis therapy and the need for personalized treatments.
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Affiliation(s)
- Gabriella Bottari
- Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Piazzale Sant'Onofrio 65, Rome, Italy.
| | - Vito Marco Ranieri
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University Aldo Moro Bari, Bari, Italy
- Department of Anesthesia and Critical Care Medicine, Policlinico Bari, Bari, Italy
| | - Can Ince
- Laboratory of Translational Intensive Care, Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Antonio Pesenti
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Filippo Aucella
- Nephrology and Dialysis Unit, Casa Solievo Della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | | | - Claudio Ronco
- International Renal Research Institute Vicenza, IRRIV, Vicenza, Italy
| | - Jean-Louis Vincent
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
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2
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Mehta Y, Paul R, Ansari AS, Banerjee T, Gunaydin S, Nassiri AA, Pappalardo F, Premužić V, Sathe P, Singh V, Vela ER. Extracorporeal blood purification strategies in sepsis and septic shock: An insight into recent advancements. World J Crit Care Med 2023; 12:71-88. [PMID: 37034019 PMCID: PMC10075046 DOI: 10.5492/wjccm.v12.i2.71] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/05/2023] [Accepted: 02/17/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Despite various therapies to treat sepsis, it is one of the leading causes of mortality in the intensive care unit patients globally. Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies (ECT) which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators.
AIM To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes.
METHODS In this review, an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis. A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts.
RESULTS Results showed that ECT techniques such as high-volume hemofiltration, coupled plasma adsorption/filtration, resin or polymer adsorbers, and CytoSorb® are emerging as adjunct therapies to improve hemodynamic stability in sepsis. CytoSorb® has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores, lactate levels, total leucocyte count, platelet count, interleukin- IL-6, IL-10, and TNF levels.
CONCLUSION Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials. In addition to patient-tailored therapies, future research developments with therapies targeting the cellular level of the immune response are expected.
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Affiliation(s)
- Yatin Mehta
- Institute of Critical Care and Anesthesiology, Medanta the Medicity, Gurugram 12201, India
| | - Rajib Paul
- Department of Internal Medicine, Apollo Hospitals, Jubilee Hills, Hyderabad 500033, India
| | - Abdul Samad Ansari
- Department of Critical Care, Nanavati Max Super Specialty Hospital, Mumbai 400065, India
| | - Tanmay Banerjee
- Department of Internal Medicine & Critical Care, Medica Institute of Critical Care Medicine, Medica Superspecialty Hospital, Kolkata 700099, India
| | - Serdar Gunaydin
- Department of Cardiovascular Surgery, University of Health Sciences, Ankara City Hospital Campus, Ankara 06933, Turkey
| | - Amir Ahmad Nassiri
- Department of Nephrology, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Federico Pappalardo
- Cardiothoracic and Vascular Anesthesia and Intensive Care, AO SS Antonio e Biagio e Cesare Arrigo, Alessandria 15121, Italy
| | - Vedran Premužić
- Department of Nephrology, Clinical Hospital Zagreb, Clinic for internal diseases, Zagreb 10000, Croatia
| | - Prachee Sathe
- Department of Critical Care Medicine, D.Y. Patil Medical College, Sant Tukaram Nagar, Pimpri Colony, Pimpri-Chinchwad, Pune 411018, India
| | - Vinod Singh
- Department of Critical Care Medicine, Institute of critical care Medicine, Hospital Name - Sir Ganga Ram Hospital, New Delhi 110001, India
| | - Emilio Rey Vela
- Cardiac Surgery Intensive Care Unit, Samaritan University Hospital, Bogotá 11, Colombia
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3
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Prado Y, Echeverría C, Feijóo CG, Riedel CA, Cabello-Verrugio C, Santibanez JF, Simon F. Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats. Antioxidants (Basel) 2023; 12:659. [PMID: 36978907 PMCID: PMC10044831 DOI: 10.3390/antiox12030659] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/03/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment.
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Affiliation(s)
- Yolanda Prado
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370186, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
| | - Cesar Echeverría
- Laboratory of Molecular Biology, Nanomedicine and Genomics, Faculty of Medicine, University of Atacama, Copiapo 1532502, Chile
| | - Carmen G. Feijóo
- Fish Immunology Laboratory, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370186, Chile
| | - Claudia A. Riedel
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Laboratory of Endocrinology-Immunology, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370186, Chile
| | - Claudio Cabello-Verrugio
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370186, Chile
- Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago 8350709, Chile
| | - Juan F. Santibanez
- Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
- Integrative Center for Biology and Applied Chemistry (CIBQA), Bernardo O’Higgins University, Santiago 8370993, Chile
| | - Felipe Simon
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370186, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Millennium Nucleus of Ion Channel-Associated Diseases, Santiago 8380453, Chile
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Rojas M, Prado Y, Tapia P, Carreño LJ, Cabello-Verrugio C, Simon F. Oxidized High-Density Lipoprotein Induces Endothelial Fibrosis Promoting Hyperpermeability, Hypotension, and Increased Mortality. Antioxidants (Basel) 2022; 11:2469. [PMID: 36552677 PMCID: PMC9774523 DOI: 10.3390/antiox11122469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
During systemic inflammation, reactive oxygen species (ROS) are generated in the bloodstream, producing large amounts of oxidized HDL (oxHDL). OxHDL loses the vascular protective features of native HDL, acquiring detrimental actions. Systemic inflammation promotes endothelial fibrosis, characterized by adhesion protein downregulation and fibrotic-specific gene upregulation, disrupting endothelial monolayer integrity. Severe systemic inflammatory conditions, as found in critically ill patients in the intensive care unit (ICU), exhibit endothelial hyperpermeability, hypotension, and organ hypoperfusion, promoting organ dysfunction and increased mortality. Because endothelial fibrosis disturbs the endothelium, it is proposed that it is the cellular and molecular origin of endothelial hyperpermeability and the subsequent deleterious consequences. However, whether oxHDL is involved in this process is unknown. The aim of this study was to investigate the fibrotic effect of oxHDL on the endothelium, to elucidate the underlying molecular and cellular mechanism, and to determine its effects on vascular permeability, blood pressure, and mortality. The results showed that oxHDL induces endothelial fibrosis through the LOX-1/NOX-2/ROS/NF-κB pathway, TGF-β secretion, and ALK-5/Smad activation. OxHDL-treated rats showed endothelial hyperpermeability, hypotension, and an enhanced risk of death and mortality, which was prevented using an ALK-5 inhibitor and antioxidant diet consumption. Additionally, the ICU patients showed fibrotic endothelial cells, and the resuscitation fluid volume administered correlated with the plasma oxHDL levels associated with an elevated risk of death and mortality. We conclude that oxHDL generates endothelial fibrosis, impacting blood pressure regulation and survival.
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Affiliation(s)
- Macarena Rojas
- Laboratory of Integrative Physiopathology, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile
| | - Yolanda Prado
- Laboratory of Integrative Physiopathology, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
| | - Pablo Tapia
- Unidad de Paciente Crítico Adulto, Hospital Clínico La Florida, La Florida, Santiago 8242238, Chile
| | - Leandro J. Carreño
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
| | - Claudio Cabello-Verrugio
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile
- Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago 9170020, Chile
| | - Felipe Simon
- Laboratory of Integrative Physiopathology, Faculty of Life Science, Universidad Andres Bello, Santiago 8370186, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Santiago 8380453, Chile
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5
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López R, Pérez-Araos R, Salazar Á, Espinoza M, Vial C, Cuiza A, Vial PA, Graf J. Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome. J Med Virol 2021; 93:4738-4747. [PMID: 33710670 PMCID: PMC8359853 DOI: 10.1002/jmv.26930] [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: 07/17/2020] [Revised: 03/02/2021] [Accepted: 03/07/2021] [Indexed: 12/15/2022]
Abstract
Background Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. Methods We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF‐responders if VA ECMO was avoided and HVHF‐nonresponders if VA ECMO support was needed despite HVHF. A targeted‐HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients. Results Patients had maximum serum lactate of 8.8 (8.7–12.8) mmol/L and a lowest cardiac index of 1.8 (1.8–1.9) L/min/m2. The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF‐responders who received targeted‐HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication. Conclusion HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted‐HVHF may increase the chance of success.
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Affiliation(s)
- René López
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago, Chile.,Carrera de Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Rodrigo Pérez-Araos
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago, Chile.,Carrera de Kinesiología, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Álvaro Salazar
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago, Chile
| | - Mauricio Espinoza
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago, Chile.,Carrera de Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Cecilia Vial
- Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile
| | - Analia Cuiza
- Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile
| | - Pablo A Vial
- Carrera de Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.,Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.,Departamento de Pediatría, Clínica Alemana de Santiago, Santiago, Chile
| | - Jerónimo Graf
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago, Chile.,Carrera de Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
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6
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Zhang L, Feng Y, Fu P. Blood purification for sepsis: an overview. PRECISION CLINICAL MEDICINE 2021; 4:45-55. [PMID: 35693122 PMCID: PMC8982546 DOI: 10.1093/pcmedi/pbab005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/09/2021] [Accepted: 02/17/2021] [Indexed: 02/05/2023] Open
Abstract
Sepsis is a life-threatening organ failure exacerbated by a maladaptive infection response from the host, and is one of the major causes of mortality in the intensive care unit. In recent decades, several extracorporeal blood purification techniques have been developed to manage sepsis by acting on both the infectious agents themselves and the host immune response. This research aims to summarize recent progress on extracorporeal blood purification technologies applied for sepsis, discuss unanswered questions on renal replacement therapy for septic patients, and present a decision-making strategy for practitioners.
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Affiliation(s)
- Ling Zhang
- Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yuying Feng
- Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Ping Fu
- Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China
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7
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Ramírez-Guerrero G, Torres Cifuentes V, Baghetti Hernández R, Villagrán Cortés F, Rojas Doll S, Oliva Alarcón R, Lucero Córdova C, Flores Fernandez P, Garay Coloma O. Early Cytokine Removal in Critical COVID-19 Patients with Extracorporeal Therapies (HA-380 plus High Volume Hemofiltration) May Prevent Progression of Acute Respiratory Distress Syndrome: Case Report. Blood Purif 2020; 50:575-577. [PMID: 33264786 PMCID: PMC7801985 DOI: 10.1159/000512982] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 11/09/2020] [Indexed: 11/19/2022]
Abstract
We present the case of a patient who suffered from acute respiratory distress syndrome caused by pneumonia associated with COVID-19 and cytokine release syndrome. This patient received a high-volume hemofiltration plus adsorption, solving the hemodynamic deterioration, pulmonary infiltrates, and gas exchange. Our clinical case proposes that the extracorporeal therapies can have a role in the management of severe COVID-19.
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Affiliation(s)
- Gonzalo Ramírez-Guerrero
- Critical Care Unit, Carlos Van Buren Hospital, Valparaíso, Chile, .,Dialysis and Renal Trasplant Unit, Carlos Van Buren Hospital, Valparaíso, Chile,
| | - Vicente Torres Cifuentes
- Critical Care Unit, Carlos Van Buren Hospital, Valparaíso, Chile.,Dialysis and Renal Trasplant Unit, Carlos Van Buren Hospital, Valparaíso, Chile
| | | | - Francisco Villagrán Cortés
- Critical Care Unit, Carlos Van Buren Hospital, Valparaíso, Chile.,Dialysis and Renal Trasplant Unit, Carlos Van Buren Hospital, Valparaíso, Chile
| | - Simón Rojas Doll
- Critical Care Unit, Carlos Van Buren Hospital, Valparaíso, Chile
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Abstract
Sepsis is the primary cause of acute kidney injury in critically ill patients. During the past decades, several extracorporeal blood purification techniques have been developed for sepsis and sepsis-induced acute kidney injury management. These therapies could act on both the infectious agent itself and the host immune response. In this article, we review the available literature discussing the different extracorporeal blood purification techniques, including high-volume hemofiltration, cascade hemofiltration, hemoperfusion, coupled plasma filtration adsorption, plasma exchange, and specific optimized renal replacement therapy membranes.
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Affiliation(s)
- Thibaut Girardot
- Anesthesiology and Intensive Care Medicine, Edouard Herriot Hospital, Lyon, France; EA 7426 PI3 (Pathophysiology of Injury‑Induced Immunosuppression), Claude Bernard University Lyon 1, Biomérieux, Hospices Civils de Lyon, Lyon, France.
| | - Antoine Schneider
- Intensive Care Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Thomas Rimmelé
- Anesthesiology and Intensive Care Medicine, Edouard Herriot Hospital, Lyon, France; EA 7426 PI3 (Pathophysiology of Injury‑Induced Immunosuppression), Claude Bernard University Lyon 1, Biomérieux, Hospices Civils de Lyon, Lyon, France
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9
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Escobar L, Andresen M, Downey P, Gai MN, Regueira T, Bórquez T, Lipman J, Roberts JA. Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration. Int J Antimicrob Agents 2014; 44:163-7. [PMID: 24837847 DOI: 10.1016/j.ijantimicag.2014.03.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Accepted: 03/23/2014] [Indexed: 01/24/2023]
Abstract
This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V(1)), 11.8L; volume of distribution of peripheral compartment (V(2)), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.
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Affiliation(s)
- Leslie Escobar
- Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, Santiago, Chile
| | - Max Andresen
- Department of Intensive Care Medicine, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago 8330024, Chile.
| | - Patricio Downey
- Department of Nephrology, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago, Chile
| | - Maria Nella Gai
- Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, Santiago, Chile
| | - Tomás Regueira
- Department of Intensive Care Medicine, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago 8330024, Chile
| | - Tamara Bórquez
- Department of Nephrology, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago, Chile
| | - Jeffrey Lipman
- Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia
| | - Jason A Roberts
- Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
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10
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Abstract
Cardiorenal syndrome (CRS) includes a broad spectrum of diseases within which both the heart and kidneys are involved, acutely or chronically. An effective classification of CRS in 2008 essentially divides CRS in two main groups, cardiorenal and renocardiac CRS, based on primum movens of disease (cardiac or renal); both cardiorenal and renocardiac CRS are then divided into acute and chronic, according to onset of disease. The fifth type of CRS integrates all cardiorenal involvement induced by systemic disease. This article addresses the pathophysiology, diagnosis, treatment, and outcomes of the 5 distinct types of CRS.
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Affiliation(s)
- Claudio Ronco
- International Renal Research Institute, S. Bortolo Hospital, Viale F. Ridolfi 37, Vicenza 36100, Italy
| | - Luca Di Lullo
- Department of Nephrology and Dialysis, L. Parodi-Delfino Hospital, Piazza A. Moro, Colleferro, Roma 1-00034, Italy.
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11
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Slack AJ, Auzinger G, Willars C, Dew T, Musto R, Corsilli D, Sherwood R, Wendon JA, Bernal W. Ammonia clearance with haemofiltration in adults with liver disease. Liver Int 2014; 34:42-8. [PMID: 23786538 DOI: 10.1111/liv.12221] [Citation(s) in RCA: 111] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 05/11/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. METHODS Prospective study of adult patients with liver failure and arterial ammonia >100 μmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. RESULTS Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) μmol/L, (P ≤ 0.0001). CONCLUSION Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration.
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Affiliation(s)
- Andrew J Slack
- Institute of Liver Studies, King's College Hospital Foundation Trust, London, UK
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